rqh1

UniProt ID: Q09811
Organism: Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Review Status: DRAFT
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Gene Description

Rqh1 (also known as rad12, hus2 and rec9) is the single RecQ-family ATP-dependent 3'-5' DNA helicase of Schizosaccharomyces pombe, orthologous to Saccharomyces cerevisiae Sgs1 and to the human RecQ helicases BLM, WRN and RECQL4. The 1328-residue protein contains a central SF2 helicase core (Walker-A ATP-binding motif and DEAH box), a RecQ-specific RQC/zinc-binding region and a C-terminal HRDC domain. It couples ATP hydrolysis to 3'-to-5' unwinding of duplex DNA (EC 5.6.2.4) and functions chiefly in the nucleus, including nuclear chromosomes, the nucleolus, replication forks and sites of DNA double-strand breaks. Rqh1 forms a high-molecular-weight complex with topoisomerase III (Top3), binding Top3 through its N-terminal region; this RecQ-Top3 complex maintains genome stability by suppressing inappropriate and hyper-recombination, by processing stalled and collapsed replication forks so that they restart without generating one-sided breaks and deletions, by dissolving/disassembling recombination intermediates such as D-loops and double Holliday junctions, and by contributing to homologous-recombination repair of double-strand breaks. Rqh1 also acts in the S-phase DNA-damage checkpoint (replication slowing) and in maintenance of the ribosomal DNA repeats and faithful chromosome segregation. Loss of Rqh1 causes hydroxyurea and UV sensitivity, elevated recombination and chromosome loss, and aberrant mitosis.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005737 cytoplasm
IBA
GO_REF:0000033 		REMOVE
Summary: Phylogenetic (IBA) propagation of cytoplasmic localization across the RecQ family. Rqh1 is a DNA helicase that acts on nuclear chromosomal DNA; all experimental S. pombe data localize it to the nucleus, nuclear chromosome, nucleolus, replication forks and DSB sites. There is no experimental support for a cytoplasmic site of action, so this generic IBA term is an over-annotation for this gene.
Reason: Contradicted by experimental localization; Rqh1 acts in the nucleus, not the cytoplasm. The IBA cytoplasm term derives from family-wide propagation and is not supported for this nuclear DNA helicase.
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0006260 DNA replication
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Rqh1 acts at DNA replication forks, processing stalled and collapsed forks to allow recovery and restart. The broad term DNA replication is acceptable but the more specific replication-fork processing terms (annotated separately) better capture its role.
Reason: Generic phylogenetic term; Rqh1's replication-associated role is real but more precisely captured by replication fork processing terms. Retained as non-core to avoid implying a core replicative-helicase function.
Supporting Evidence:
PMID:15889146
These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.
GO:0005634 nucleus
IBA
GO_REF:0000033 		ACCEPT
Summary: Nuclear localization is strongly supported experimentally for Rqh1 and is consistent with its function as a chromosomal DNA helicase.
Reason: Corroborated by experimental nuclear localization in S. pombe.
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0005694 chromosome
IBA
GO_REF:0000033 		ACCEPT
Summary: Rqh1 acts on chromosomal DNA; experimental data localize it to nuclear chromosomes. The IBA chromosome term is consistent with the more specific experimental nuclear chromosome annotation.
Reason: Consistent with experimental nuclear chromosome localization (IDA, PMID:12724426).
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0000166 nucleotide binding
IEA
GO_REF:0000002 		MODIFY
Summary: Generic InterPro-derived term. Rqh1 binds and hydrolyzes ATP, so it is a nucleotide-binding protein, but the specific term ATP binding (also annotated) is far more informative and should be preferred.
Reason: Too general; ATP binding is the specific, experimentally supported MF for this RecQ helicase and is already present.
Proposed replacements: ATP binding
Supporting Evidence:
PMID:12478586
Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
GO:0000724 double-strand break repair via homologous recombination
IEA
GO_REF:0000117 		ACCEPT
Summary: Rqh1 participates in homologous-recombination repair of double-strand breaks (e.g. in G2 after UV/IR), acting downstream of Rad51/Rhp51 to process recombination intermediates. This IEA duplicates the experimentally supported IMP/IGI annotations.
Reason: Corroborated by experimental IMP/IGI annotations to the same term in S. pombe.
Supporting Evidence:
PMID:12724426
Our data provide evidence that Rqh1 functions after Rad51 focus formation during DNA repair.
GO:0000729 DNA double-strand break processing
IEA
GO_REF:0000117 		ACCEPT
Summary: Rqh1 (the Sgs1 ortholog) contributes to long-range end resection at DSBs, though in fission yeast this is a minor role with Exo1 dominant. This IEA duplicates the experimentally supported IMP annotation.
Reason: Corroborated by experimental IMP annotation (PMID:21931565).
Supporting Evidence:
PMID:21931565
Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role.
GO:0003676 nucleic acid binding
IEA
GO_REF:0000002 		MODIFY
Summary: Very general InterPro term. Rqh1 binds DNA specifically; the DNA binding term (also annotated) is the appropriate, more informative MF.
Reason: Too general; DNA binding is the specific supported molecular function.
Proposed replacements: DNA binding
Supporting Evidence:
PMID:15702347
The Schizosaccharomyces pombe rqh1+ gene encodes a member of the RecQ DNA helicase family.
GO:0003677 DNA binding
IEA
GO_REF:0000117 		ACCEPT
Summary: Rqh1 is a DNA helicase that binds and translocates on DNA. DNA binding is a well-supported molecular function.
Reason: Consistent with helicase activity and the TAS DNA-binding annotation.
Supporting Evidence:
PMID:12478586
Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
GO:0004386 helicase activity
IEA
GO_REF:0000002 		MODIFY
Summary: Rqh1 is a helicase, but the experimentally demonstrated specific activity is ATP-dependent 3'-5' DNA helicase activity. The generic helicase term should be refined to the specific child term.
Reason: Too general; biochemical data establish 3'-5' DNA helicase activity (GO:0043138), which is already annotated experimentally.
Proposed replacements: 3'-5' DNA helicase activity
Supporting Evidence:
PMID:12478586
Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
GO:0005524 ATP binding
IEA
GO_REF:0000002 		ACCEPT
Summary: Rqh1 contains a Walker-A ATP-binding motif and couples ATP binding/ hydrolysis to DNA unwinding; ATP binding is a core molecular function.
Reason: Supported by the conserved ATP-binding motif and the demonstrated ATP-dependent helicase activity.
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0005634 nucleus
IEA
GO_REF:0000120 		ACCEPT
Summary: Duplicate nuclear-localization annotation (UniProt automatic). Supported by the experimental EXP/IDA nuclear localization for Rqh1.
Reason: Corroborated by experimental nuclear localization (PMID:12724426).
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0006260 DNA replication
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: InterPro-derived duplicate of the DNA replication annotation. Rqh1 acts at replication forks; the more specific fork-processing terms are preferred.
Reason: Generic term; replication-associated role is better captured by replication fork processing terms.
Supporting Evidence:
PMID:15889146
These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.
GO:0006281 DNA repair
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: Rqh1 is required for DNA repair, especially recombination-mediated repair of UV/IR damage and processing of damaged replication forks. The general DNA repair term is correct but less informative than the specific recombination/fork-processing terms annotated elsewhere.
Reason: Correct but general parent term; specific DSB-repair-via-HR and fork processing terms better represent the core function.
Supporting Evidence:
PMID:9372918
We show that Rqhl is involved in a DNA damage survival mechanism which prevents cell death when UV-induced DNA damage cannot be removed.
GO:0006310 DNA recombination
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: Rqh1 is centrally involved in DNA recombination, principally as a negative regulator/anti-recombinase that suppresses inappropriate and hyper-recombination and dissolves recombination intermediates. The general term is correct; more specific child terms are annotated experimentally.
Reason: Correct but general parent; specific terms (resolution of recombination intermediates, recombinational repair) capture the core role.
Supporting Evidence:
PMID:19037101
the helicase Rqh1, which are implicated in replication fork stability and the negative regulation of recombination.
GO:0006312 mitotic recombination
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Rqh1 acts in mitotically dividing cells to control recombination at stalled forks and DSBs, and to process mitotic recombination intermediates. The term is appropriate; more specific child terms are annotated.
Reason: Correct but general; resolution of mitotic recombination intermediates and mitotic recombination-dependent fork processing are the specific terms.
Supporting Evidence:
PMID:23093942
Rqh1 limits GCRs at collapsed forks by preventing inappropriate ectopic recombination during the process of fork recovery by recombination proteins.
GO:0016887 ATP hydrolysis activity
IEA
GO_REF:0000116 		ACCEPT
Summary: Rqh1 is an ATP-dependent helicase (EC 5.6.2.4) that hydrolyzes ATP to power 3'-5' translocation; ATP hydrolysis is an intrinsic core activity.
Reason: Supported by the ATP-dependent helicase mechanism and RHEA EC mapping.
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0031422 RecQ family helicase-topoisomerase III complex
IEA
GO_REF:0000117 		ACCEPT
Summary: Rqh1 forms a high-molecular-weight complex with topoisomerase III (Top3), the defining RecQ-Top3 complex. Well supported experimentally.
Reason: Corroborated by experimental IDA/NAS annotations for the RecQ-Top3 complex.
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0031573 mitotic intra-S DNA damage checkpoint signaling
IEA
GO_REF:0000117 		ACCEPT
Summary: Rqh1 is required, in an epistatic pathway with Mus81 and Rhp51 downstream of Cds1, for slowing replication in response to S-phase DNA damage. This IEA duplicates the experimentally supported IMP annotations.
Reason: Corroborated by experimental IMP annotations (PMID:19037101).
Supporting Evidence:
PMID:19037101
We have identified proteins downstream of Cds1 required for checkpoint-dependant slowing, including the structure-specific endonuclease Mus81 and the helicase Rqh1.
GO:0043138 3'-5' DNA helicase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Core molecular function: ATP-dependent 3'-5' DNA helicase activity, shown biochemically. This IEA matches the experimental IDA annotations.
Reason: Corroborated by experimental IDA biochemical demonstration.
Supporting Evidence:
PMID:12478586
Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
GO:0031422 RecQ family helicase-topoisomerase III complex
NAS
PMID:15702347
The N-terminal region of the Schizosaccharomyces pombe RecQ ... 		ACCEPT
Summary: The N-terminal region of Rqh1 physically binds Top3, supporting membership in the RecQ-Top3 complex. Consistent with the IDA complex annotation.
Reason: Supported by demonstrated physical Top3 binding via the Rqh1 N-terminus.
Supporting Evidence:
PMID:15702347
Topoisomerase III (Top3) binds to a site within the first 322 N-terminal amino acids of Rqh1 and that this binding correlates with Rqh1 function.
GO:0005634 nucleus
EXP
PMID:12724426
Role for the fission yeast RecQ helicase in DNA repair in G2... 		ACCEPT
Summary: Experimental (EXP) nuclear localization of Rqh1 in S. pombe. This is the primary, well-supported localization for the protein.
Reason: Direct experimental evidence for nuclear localization.
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0043007 maintenance of rDNA
IMP
PMID:14528010
Slx1-Slx4 are subunits of a structure-specific endonuclease ... 		ACCEPT
Summary: Deletion of Rqh1 causes contraction of the rDNA repeats, and rqh1 is synthetically lethal with the Slx1-Slx4 endonuclease, demonstrating a role in maintaining rDNA copy number at the replication fork barriers in the rDNA locus.
Reason: Direct mutant-phenotype evidence for rDNA maintenance.
Supporting Evidence:
PMID:14528010
Deletion of Slx1 or Rqh1 RecQ-like DNA helicase provokes rDNA contraction, whereas simultaneous elimination of Slx1-Slx4 endonuclease and Rqh1 is lethal.
GO:1990426 mitotic recombination-dependent replication fork processing
IMP
PMID:30667359
Factors affecting template switch recombination associated w... 		ACCEPT
Summary: Rqh1, together with Fbh1 and Srs2, strongly suppresses template switching during recombination-restarted replication, a key aspect of processing restarted forks. Direct mutant evidence.
Reason: Direct genetic evidence that Rqh1 suppresses template switching at restarted forks.
Supporting Evidence:
PMID:30667359
A further three conserved helicases (Fbh1, Rqh1 and Srs2) strongly suppress TS, but there is no change in TS frequency in cells lacking Fml1 or Mus81.
GO:0000729 DNA double-strand break processing
IMP
PMID:21931565
Release of Ku and MRN from DNA ends by Mre11 nuclease activi... 		ACCEPT
Summary: Rqh1 (Sgs1 ortholog) contributes to extended end resection at DSBs, supporting Exo1-dependent long-range resection, although it plays a minor role relative to Exo1 in fission yeast.
Reason: Direct evidence for a (minor) role in DSB end resection/processing.
Supporting Evidence:
PMID:21931565
Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role.
GO:0000724 double-strand break repair via homologous recombination
IMP
PMID:12023299
Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomer... 		ACCEPT
Summary: Rqh1, in association with Top3, processes recombination intermediates during HR repair of radiation-induced DSBs in G2, acting after the assembly of Rhp51 (Rad51) foci. Core DSB-repair function.
Reason: Direct mutant evidence for a role in HR repair of DSBs in G2.
Supporting Evidence:
PMID:12023299
low Cdc2-cyclin B activity prevents the proper regulation of topoisomerase III (Top3) function, disrupting a recombination step that occurs after the assembly of Rhp51 foci.
GO:0000724 double-strand break repair via homologous recombination
IGI
PMID:12023299
Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomer... 		ACCEPT
Summary: Genetic-interaction evidence (with crb2/rad50 partners) places Rqh1-Top3 in the HR pathway for repairing G2 DSBs, downstream of Rhp51 focus assembly. Consistent with the IMP annotation to the same term.
Reason: Genetic-interaction evidence supports the HR DSB-repair role.
Supporting Evidence:
PMID:12023299
low Cdc2-cyclin B activity prevents the proper regulation of topoisomerase III (Top3) function, disrupting a recombination step that occurs after the assembly of Rhp51 foci.
GO:0005730 nucleolus
IDA
PMID:12023299
Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomer... 		ACCEPT
Summary: Rqh1 localizes to the nucleolus, consistent with its role in maintaining the rDNA repeats located there. Direct localization evidence.
Reason: Direct experimental nucleolar localization, consistent with rDNA maintenance.
Supporting Evidence:
PMID:12023299
The availability of a sister chromatid, and thus the cell cycle phase in which DNA double-strand breaks (DSBs) occur, influences the choice between homologous recombination (HR) or nonhomologous end joining (NHEJ).
GO:0035861 site of double-strand break
IDA
PMID:12023299
Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomer... 		ACCEPT
Summary: Rqh1 is recruited to sites of DNA double-strand breaks, consistent with its role in HR repair downstream of Rhp51 focus formation.
Reason: Direct localization evidence to DSB sites; consistent with its HR repair role.
Supporting Evidence:
PMID:12023299
disrupting a recombination step that occurs after the assembly of Rhp51 foci.
GO:0031573 mitotic intra-S DNA damage checkpoint signaling
IMP
PMID:19037101
Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway requ... 		ACCEPT
Summary: Rqh1 functions in an epistatic pathway with Mus81 and Rhp51, downstream of the checkpoint kinase Cds1, that is required for slowing replication in response to S-phase DNA damage. Direct mutant evidence.
Reason: Direct mutant evidence for a role in the intra-S DNA damage checkpoint (replication slowing).
Supporting Evidence:
PMID:19037101
We have identified proteins downstream of Cds1 required for checkpoint-dependant slowing, including the structure-specific endonuclease Mus81 and the helicase Rqh1.
GO:1990426 mitotic recombination-dependent replication fork processing
IDA
PMID:25313826
The chromatin assembly factor 1 promotes Rad51-dependent tem... 		ACCEPT
Summary: Rqh1 disassembles recombination D-loops formed during Rad51-dependent template switching at blocked forks; CAF-1 antagonizes this disassembly. Direct physical-assay evidence for fork-intermediate processing.
Reason: Direct (physical assay) evidence that Rqh1 disassembles D-loops at restarted forks.
Supporting Evidence:
PMID:25313826
We establish that CAF-1 promotes template switch by counteracting D-loop disassembly by Rqh1.
GO:0070914 UV-damage excision repair
IMP
PMID:7623848
An alternative eukaryotic DNA excision repair pathway. 		MARK AS OVER ANNOTATED
Summary: This annotation derives from the rad12-502 allele, which was reported to lack the SPDE UV-dimer endonuclease activity of an alternative excision repair pathway. However, the same gene was subsequently shown to be the RecQ helicase rqh1/hus2, and a later study explicitly could not reproduce a UV-dimer endonuclease defect in rqh1 (rad12) mutants. The excision (SPDE) activity is not a property of the RecQ helicase, and Rqh1's true UV role is in recombination-based damage tolerance/bypass during S phase. This is best regarded as an over-annotation (historic misattribution of a distinct excision-repair endonuclease function to Rqh1).
Reason: The SPDE/UV-dimer excision activity attributed to the rad12-502 strain is not a function of the RecQ helicase and was later refuted; Rqh1's UV role is in recombination/replication-bypass damage tolerance, not excision repair. Per the do-not-overrule rule this is downgraded rather than removed, as the rad12-502 phenotype is genuine even if mechanistically reassigned.
Supporting Evidence:
PMID:7623848
Here we report that the UV-sensitive S. pombe rad12-502 mutant lacks SPDE activity.
PMID:9372918
in contrast with the reported literature, we do not find that rqh1 (rad12) mutant cells are defective in UV dimer endonuclease activity.
GO:1990426 mitotic recombination-dependent replication fork processing
IMP
PMID:23093942
Recovery of arrested replication forks by homologous recombi... 		ACCEPT
Summary: Rqh1 limits gross chromosomal rearrangements at collapsed forks by preventing inappropriate ectopic recombination during HR-mediated fork recovery. Direct mutant evidence for fork processing.
Reason: Direct mutant evidence for Rqh1 in processing recombination-restarted forks.
Supporting Evidence:
PMID:23093942
Rqh1 limits GCRs at collapsed forks by preventing inappropriate ectopic recombination during the process of fork recovery by recombination proteins.
GO:0000228 nuclear chromosome
IDA
PMID:12724426
Role for the fission yeast RecQ helicase in DNA repair in G2... 		ACCEPT
Summary: Rqh1 localizes to and acts on nuclear chromosomes, consistent with its role as a chromosomal DNA helicase in DNA repair and recombination.
Reason: Direct experimental nuclear-chromosome localization.
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0005730 nucleolus
IDA
PMID:12724426
Role for the fission yeast RecQ helicase in DNA repair in G2... 		ACCEPT
Summary: Nucleolar localization consistent with the role of the Rqh1-Top3 complex in maintaining rDNA repeat structure. Direct localization evidence.
Reason: Direct experimental nucleolar localization, consistent with rDNA maintenance.
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0006301 DNA damage tolerance
IMP
PMID:12724426
Role for the fission yeast RecQ helicase in DNA repair in G2... 		ACCEPT
Summary: Rqh1 is required for survival of UV-induced DNA damage that cannot be removed, operating in S phase as part of a damage-tolerance/bypass mechanism. Direct mutant evidence (rqh1 deletion is UV/HU sensitive).
Reason: Direct mutant-phenotype evidence for a role in DNA damage tolerance.
Supporting Evidence:
PMID:9372918
We show that Rqhl is involved in a DNA damage survival mechanism which prevents cell death when UV-induced DNA damage cannot be removed.
GO:0043138 3'-5' DNA helicase activity
IDA
PMID:12724426
Role for the fission yeast RecQ helicase in DNA repair in G2... 		ACCEPT
Summary: Core molecular function. Rqh1 was directly shown to be a 3'-to-5' DNA helicase; T543I and K547A/R mutations abolish this activity.
Reason: Direct biochemical demonstration of 3'-5' DNA helicase activity.
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0031297 replication fork processing
IGI
PMID:16303848
A role for the fission yeast Rqh1 helicase in chromosome seg... 		ACCEPT
Summary: Rqh1 (the Top3-RecQ complex) processes aberrant chromosome structures arising from DNA replication, particularly at the rDNA replication fork barriers; rqh1 deletion causes anaphase delay and lagging rDNA.
Reason: Genetic-interaction evidence (reb1 suppression) for fork processing at the rDNA locus.
Supporting Evidence:
PMID:16303848
These data are consistent with the function of the Top3-RecQ complex in maintenance of the rDNA structure by processing aberrant chromosome structures arising from DNA replication.
GO:0043007 maintenance of rDNA
IMP
PMID:16303848
A role for the fission yeast Rqh1 helicase in chromosome seg... 		ACCEPT
Summary: rqh1 deletion produces lagging chromosomal DNA especially at the rDNA locus and anaphase delay; relieving rDNA fork arrest (reb1 deletion) partially suppresses these phenotypes, supporting a role in rDNA maintenance via the Top3-RecQ complex.
Reason: Direct mutant evidence for rDNA maintenance (also independently supported by PMID:14528010).
Supporting Evidence:
PMID:16303848
relieving replication fork arrest in the rDNA repeat by deletion of reb1+ partially suppresses rqh1delta phenotypes.
GO:0071140 resolution of mitotic recombination intermediates
IMP
PMID:15889146
Replication fork blockage by RTS1 at an ectopic site promote... 		ACCEPT
Summary: Rqh1 acts to prevent blocked replication forks from collapsing and generating one-sided DSBs and deletion events at the RTS1 fork barrier, consistent with resolving/dissolving recombination intermediates at stalled forks. Direct mutant evidence.
Reason: Direct mutant evidence that Rqh1 resolves recombination intermediates at blocked forks.
Supporting Evidence:
PMID:15889146
In the absence of the RecQ family DNA helicase Rqh1, deletion events increase dramatically, which correlates with the detection of one-sided DNA double-strand breaks at or near RTS1. These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.
GO:0000725 recombinational repair
IGI
PMID:16135799
Role of the Schizosaccharomyces pombe F-Box DNA helicase in ... 		ACCEPT
Summary: Rqh1 functions in processing recombination intermediates; the fbh1 F-box helicase is synthetically lethal with rqh1 (and srs2), with lethality suppressed by rhp57 deletion, indicating overlapping roles in resolving toxic Rhp51-dependent recombination intermediates.
Reason: Genetic-interaction (synthetic lethality with fbh1) evidence for recombinational repair.
Supporting Evidence:
PMID:16135799
fbh1 is essential for viability in stationary-phase cells and in the absence of either Srs2 or Rqh1 DNA helicase. In each case, lethality is suppressed by deletion of the recombination gene rhp57.
GO:0006974 DNA damage response
IMP
PMID:9372918
Role of Schizosaccharomyces pombe RecQ homolog, recombinatio... 		KEEP AS NON CORE
Summary: Rqh1 operates during S phase as part of a DNA damage survival mechanism requiring the recombination machinery, the checkpoint rad genes and Cds1. The broad DNA damage response term is correct but general; specific checkpoint and recombination terms are annotated separately.
Reason: Correct but general parent term; more specific checkpoint and damage-tolerance terms capture the core role.
Supporting Evidence:
PMID:9372918
Our data suggest that Rqh1 operates during S phase as part of a mechanism which prevents DNA damage causing cell lethality.
GO:0003677 DNA binding
TAS
PMID:15702347
The N-terminal region of the Schizosaccharomyces pombe RecQ ... 		ACCEPT
Summary: DNA binding is well supported for this RecQ helicase that binds and translocates on DNA.
Reason: Consistent with the demonstrated DNA helicase activity.
Supporting Evidence:
PMID:15702347
The Schizosaccharomyces pombe rqh1+ gene encodes a member of the RecQ DNA helicase family.
GO:0031422 RecQ family helicase-topoisomerase III complex
IDA
PMID:12724426
Role for the fission yeast RecQ helicase in DNA repair in G2... 		ACCEPT
Summary: Direct evidence that Rqh1 exists with Top3 in a high-molecular-weight complex (the RecQ-Top3 complex). Core cellular-component assignment.
Reason: Direct experimental evidence for the Rqh1-Top3 complex.
Supporting Evidence:
PMID:12724426
We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
GO:0043138 3'-5' DNA helicase activity
IDA
PMID:12478586
Helicase activity is only partially required for Schizosacch... 		ACCEPT
Summary: Independent biochemical demonstration that Rqh1p displays 3'-5' DNA helicase activity. Core molecular function.
Reason: Direct biochemical demonstration of 3'-5' DNA helicase activity.
Supporting Evidence:
PMID:12478586
Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
GO:0043596 nuclear replication fork
IC
PMID:12724426
Role for the fission yeast RecQ helicase in DNA repair in G2... 		ACCEPT
Summary: Curator-inferred (IC, from the RecQ-Top3 complex annotation) localization to the nuclear replication fork. Consistent with Rqh1's well-documented action at stalled/collapsed replication forks.
Reason: Inference is consistent with extensive evidence that Rqh1 acts at replication forks to prevent collapse and process restarted forks.
Supporting Evidence:
PMID:15889146
These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.

Core Functions

ATP-dependent 3'-5' DNA helicase activity (EC 5.6.2.4) that unwinds duplex DNA by coupling ATP binding and hydrolysis to 3'-to-5' translocation; the enzymatic core of all Rqh1 genome-maintenance functions.

Molecular Function:
3'-5' DNA helicase activity
Directly Involved In:
DNA recombination
Cellular Locations:
nuclear chromosome
Supporting Evidence:
  • PMID:12478586
    Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
  • PMID:12724426
    We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.

Suppression of inappropriate/hyper-recombination and processing of stalled and collapsed replication forks: acting with topoisomerase III (the RecQ-Top3 complex), Rqh1 prevents blocked forks from collapsing into one-sided breaks, dissolves/disassembles recombination intermediates (D-loops, double Holliday junctions), and suppresses error-prone template switching during recombination-mediated fork restart.

Molecular Function:
3'-5' DNA helicase activity
Directly Involved In:
mitotic recombination-dependent replication fork processing resolution of mitotic recombination intermediates
Cellular Locations:
nuclear replication fork
Supporting Evidence:
  • PMID:15889146
    These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.
  • PMID:25313826
    We establish that CAF-1 promotes template switch by counteracting D-loop disassembly by Rqh1.
  • PMID:30667359
    A further three conserved helicases (Fbh1, Rqh1 and Srs2) strongly suppress TS, but there is no change in TS frequency in cells lacking Fml1 or Mus81.

Homologous-recombination repair of DNA double-strand breaks and DNA damage tolerance: Rqh1 contributes (minor role) to long-range end resection and, chiefly, processes recombination intermediates downstream of Rhp51/Rad51 during G2 HR repair, enabling survival of UV/IR damage.

Molecular Function:
3'-5' DNA helicase activity
Directly Involved In:
double-strand break repair via homologous recombination DNA damage tolerance
Cellular Locations:
site of double-strand break
Supporting Evidence:
  • PMID:12724426
    Our data provide evidence that Rqh1 functions after Rad51 focus formation during DNA repair.
  • PMID:21931565
    Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role.
  • PMID:9372918
    We show that Rqhl is involved in a DNA damage survival mechanism which prevents cell death when UV-induced DNA damage cannot be removed.

Maintenance of ribosomal DNA repeats and faithful chromosome segregation: the Rqh1-Top3 complex localizes to the nucleolus and resolves aberrant structures at the rDNA replication fork barriers, preventing rDNA contraction, anaphase delay and lagging chromosomes.

Molecular Function:
3'-5' DNA helicase activity
Directly Involved In:
maintenance of rDNA
Cellular Locations:
nucleolus
Supporting Evidence:
  • PMID:14528010
    Deletion of Slx1 or Rqh1 RecQ-like DNA helicase provokes rDNA contraction, whereas simultaneous elimination of Slx1-Slx4 endonuclease and Rqh1 is lethal.
  • PMID:16303848
    These data are consistent with the function of the Top3-RecQ complex in maintenance of the rDNA structure by processing aberrant chromosome structures arising from DNA replication.

References

file:interpro/panther/PTHR13710/PTHR13710-review.md
PANTHER family review PTHR13710: IBA propagation assessment for rqh1
GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000116
Automatic Gene Ontology annotation based on Rhea mapping
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:12023299
Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomerase III.
  • Rqh1, in association with Top3, processes recombination intermediates during G2 HR repair of radiation-induced DSBs, acting after Rhp51 focus assembly and regulated by Cdc2-cyclin B via Crb2.
    "low Cdc2-cyclin B activity prevents the proper regulation of topoisomerase III (Top3) function, disrupting a recombination step that occurs after the assembly of Rhp51 foci."
PMID:12478586
Helicase activity is only partially required for Schizosaccharomyces pombe Rqh1p function.
  • Rqh1p is biochemically a 3'-5' DNA helicase, but its helicase activity is only partially required for recovery from S-phase arrest or DNA damage.
    "Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity. Interestingly, however, unlike other RecQ family members, the helicase activity of Rqh1p is only partially required for its function in recovery from S-phase arrest or DNA damage."
PMID:12724426
Role for the fission yeast RecQ helicase in DNA repair in G2.
  • Rqh1 is the single S. pombe RecQ homolog, a 3'-5' helicase that exists with Top3 in a high-MW complex and functions after Rad51 focus formation in G2 DNA repair.
    "We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex."
PMID:14528010
Slx1-Slx4 are subunits of a structure-specific endonuclease that maintains ribosomal DNA in fission yeast.
  • Deletion of Rqh1 causes rDNA contraction and is synthetically lethal with the Slx1-Slx4 endonuclease, implicating Rqh1 in rDNA maintenance at replication fork barriers.
    "Deletion of Slx1 or Rqh1 RecQ-like DNA helicase provokes rDNA contraction, whereas simultaneous elimination of Slx1-Slx4 endonuclease and Rqh1 is lethal."
PMID:15702347
The N-terminal region of the Schizosaccharomyces pombe RecQ helicase, Rqh1p, physically interacts with Topoisomerase III and is required for Rqh1p function.
  • Top3 binds within the first 322 N-terminal residues of Rqh1, and this interaction correlates with Rqh1 function.
    "Topoisomerase III (Top3) binds to a site within the first 322 N-terminal amino acids of Rqh1 and that this binding correlates with Rqh1 function."
PMID:15889146
Replication fork blockage by RTS1 at an ectopic site promotes recombination in fission yeast.
  • Rqh1 prevents blocked replication forks from collapsing into one-sided DSBs and deletions at the RTS1 fork barrier.
    "In the absence of the RecQ family DNA helicase Rqh1, deletion events increase dramatically, which correlates with the detection of one-sided DNA double-strand breaks at or near RTS1. These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events."
PMID:16135799
Role of the Schizosaccharomyces pombe F-Box DNA helicase in processing recombination intermediates.
  • The Fbh1 F-box helicase is synthetically lethal with rqh1 (and srs2), suppressed by rhp57 deletion, indicating overlapping roles in processing toxic Rhp51-dependent recombination intermediates.
    "fbh1 is essential for viability in stationary-phase cells and in the absence of either Srs2 or Rqh1 DNA helicase. In each case, lethality is suppressed by deletion of the recombination gene rhp57."
PMID:16303848
A role for the fission yeast Rqh1 helicase in chromosome segregation.
  • rqh1 deletion delays anaphase and produces lagging chromosomal DNA, especially at rDNA; the Top3-RecQ complex maintains rDNA structure by processing replication-derived aberrant structures.
    "These data are consistent with the function of the Top3-RecQ complex in maintenance of the rDNA structure by processing aberrant chromosome structures arising from DNA replication."
PMID:19037101
Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the S-phase DNA damage checkpoint.
  • Mus81, Rhp51 and Rqh1 form an epistatic pathway downstream of Cds1 required for slowing replication in response to S-phase DNA damage, with Rqh1 restraining recombination.
    "We have identified proteins downstream of Cds1 required for checkpoint-dependant slowing, including the structure-specific endonuclease Mus81 and the helicase Rqh1, which are implicated in replication fork stability and the negative regulation of recombination."
PMID:21931565
Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is required for homologous recombination repair of double-strand breaks.
  • Rqh1 (Sgs1 ortholog) plays a minor role supporting Exo1-dependent long-range end resection at DSBs in fission yeast.
    "Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role."
PMID:23093942
Recovery of arrested replication forks by homologous recombination is error-prone.
  • Rqh1 limits gross chromosomal rearrangements at collapsed forks by preventing inappropriate ectopic recombination during HR-mediated fork recovery.
    "Rqh1 limits GCRs at collapsed forks by preventing inappropriate ectopic recombination during the process of fork recovery by recombination proteins."
PMID:25313826
The chromatin assembly factor 1 promotes Rad51-dependent template switches at replication forks by counteracting D-loop disassembly by the RecQ-type helicase Rqh1.
  • Rqh1 disassembles D-loops formed during Rad51-dependent template switching at blocked forks; CAF-1 antagonizes this disassembly.
    "We establish that CAF-1 promotes template switch by counteracting D-loop disassembly by Rqh1."
PMID:30667359
Factors affecting template switch recombination associated with restarted DNA replication.
  • Rqh1, together with Fbh1 and Srs2, strongly suppresses template switching during recombination-restarted DNA replication.
    "A further three conserved helicases (Fbh1, Rqh1 and Srs2) strongly suppress TS, but there is no change in TS frequency in cells lacking Fml1 or Mus81."
PMID:7623848
An alternative eukaryotic DNA excision repair pathway.
  • The rad12-502 mutant (later identified as rqh1) was reported to lack SPDE UV-dimer endonuclease activity in an excision-repair pathway distinct from NER; this excision activity was subsequently not attributable to the RecQ helicase.
    "Here we report that the UV-sensitive S. pombe rad12-502 mutant lacks SPDE activity."
PMID:9372918
Role of Schizosaccharomyces pombe RecQ homolog, recombination, and checkpoint genes in UV damage tolerance.
  • rad12-502 and hus2.22 are alleles of the recQ homolog rqh1; Rqh1 acts in S phase in a recombination/checkpoint-dependent DNA damage survival (tolerance) mechanism, and rqh1 mutants are not defective in UV dimer endonuclease activity.
    "in contrast with the reported literature, we do not find that rqh1 (rad12) mutant cells are defective in UV dimer endonuclease activity."

Suggested Questions for Experts

Q: Is the partial dispensability of Rqh1 helicase activity for S-phase recovery explained by a structural/scaffolding role of Rqh1 in the Top3 complex, or by redundancy with other helicases (Fbh1, Srs2, Pfh1)?

Q: Does the fission-yeast Rqh1-Top3 complex include an Rmi1/RMI ortholog, and how does its composition compare to the human BLM-Top3a-RMI1-RMI2 dissolvasome?

Q: To what extent does Rqh1 perform canonical double-Holliday-junction dissolution versus D-loop disassembly/anti-recombinase activity in vivo?

Suggested Experiments

Experiment: Reconstitute the Rqh1-Top3 (and candidate Rmi1) complex and test double Holliday junction dissolution and D-loop disassembly in vitro, comparing wild-type Rqh1 with the helicase-dead K547A and Top3-binding N-terminal deletion variants.

Experiment: Use chromatin immunoprecipitation / live-cell imaging of tagged Rqh1 to map its genome-wide binding at stalled forks, the rDNA fork barriers and induced DSBs, and to define the kinetics relative to Rhp51 and Top3 foci.

Experiment: Systematically separate Rqh1 functions using separation-of-function alleles (helicase-dead, HRDC-domain mutants, Top3-binding mutants) and quantify template switching, rDNA stability, end resection and checkpoint-dependent replication slowing for each.

📚 Additional Documentation

Notes

(rqh1-notes.md)

rqh1 (Q09811, SPAC2G11.12) — curation notes

Rqh1 (aka rad12, hus2, rec9) is the single RecQ-family ATP-dependent 3'-5' DNA helicase of
Schizosaccharomyces pombe, ortholog of S. cerevisiae Sgs1 and human BLM/WRN/RECQL4.

Identity / domain architecture

  • 1328 aa. Helicase ATP-binding domain (528-707), Helicase C-terminal (728-876), HRDC (1115-1195),
    DEAH box motif (651-654), Walker A ATP-binding (555-562). RecQ Zn-binding and RQC domains
    (InterPro). [UniProt Q09811]
  • EC 5.6.2.4 (DNA helicase coupling ATP hydrolysis to 3'-5' translocation). [UniProt; PMID:12724426]

Helicase activity / biochemistry

  • Rqh1 is a 3'-to-5' DNA helicase that exists with Top3 in a high-MW complex
    PMID:12724426
  • Helicase activity confirmed biochemically; T543I (rad12 allele) and K547A/R abolish helicase activity
    [UniProt MUTAGEN 543, 547; PMID:12724426]
  • Rqh1p displays 3' to 5' DNA helicase activity but helicase activity is only PARTIALLY required for function in recovery from S-phase arrest/DNA damage
    PMID:12478586

Top3 interaction / RecQ-Top3 complex

  • top3 deletion is inviable; suppressed by loss of rqh1 helicase activity or recombination functions
    PMID:12724426
  • N-terminal region (first 322 aa) of Rqh1 binds Top3; binding correlates with Rqh1 function
    PMID:15702347
  • ComplexPortal/PomBase: RecQ family helicase-topoisomerase III complex (GO:0031422)

Subcellular localization

  • Nucleus; nuclear chromosome; nucleolus [PMID:12724426; PMID:12023299]
  • Site of double-strand break, nucleolus [PMID:12023299 IDA]
  • Nuclear replication fork inferred (IC from RecQ-Top3 complex) PMID:12724426

Recombination control / fork processing (core)

  • Rqh1 acts after Rad51 (Rhp51) focus formation, downstream of strand invasion
    PMID:12724426
  • Negatively regulates recombination; rqh1Δ shows hyper-recombination, HU and UV sensitivity; DNA damage
    sensitivity alleviated by disrupting recombination
    PMID:19037101
    PMID:19037101
  • Prevents blocked forks from collapsing; rqh1- → dramatic increase in deletion events + one-sided DSBs at RTS1 RFB
    PMID:15889146
  • Rqh1 limits gross chromosomal rearrangements (GCRs) at collapsed forks by preventing inappropriate ectopic recombination during fork recovery
    PMID:23093942
  • Rqh1 counteracts D-loop disassembly (template switch) — antagonized by CAF-1
    PMID:25313826
  • Rqh1 (with Fbh1, Srs2, Pfh1) strongly suppresses template switching during recombination-restarted replication
    PMID:30667359

DSB repair / resection

  • Rqh1 (Sgs1 ortholog) has a minor role in long-range DSB end resection; Exo1 dominant
    PMID:21931565
  • HR repair of IR-induced DSBs in G2; Rqh1-Top3 processes recombination intermediates downstream of Rhp51 foci; controlled by Cdc2-cyclin B via Crb2
    PMID:12023299
  • fbh1Δ rqh1Δ double mutant is lethal (suppressed by rhp57Δ) — overlapping roles in processing toxic recombination intermediates
    PMID:16135799

S-phase checkpoint

  • Mus81, Rhp51, Rqh1 form an epistatic pathway required for the S-phase DNA damage checkpoint (replication slowing)
    PMID:19037101
    Original gene cloning: rqh1+ required for reversible S phase arrest [PMID:9184215 title]

rDNA maintenance / chromosome segregation

  • Deletion of Slx1 or Rqh1 provokes rDNA contraction; slx1 rqh1 double is lethal
    PMID:14528010
  • rqh1Δ delayed in anaphase, lagging chromosomal DNA esp. at rDNA; relieving rDNA fork arrest (reb1Δ) partially suppresses
    PMID:16303848

UV damage tolerance / excision repair controversy

  • Rqh1 is required for UV damage tolerance/survival during S phase (bypass of damage by replication fork), requires recombination + checkpoint genes + Cds1
    PMID:9372918
  • CONTROVERSY: rad12-502 was reported to lack SPDE UV-dimer endonuclease (alternative excision repair)
    PMID:7623848
    BUT the gene's identifiers later refuted this: PMID:9372918
    => GO:0070914 UV-damage excision repair (from PMID:7623848) is likely an over-annotation/historic
    misattribution of a distinct excision-repair endonuclease function to Rqh1. Treated as
    MARK_AS_OVER_ANNOTATED (the SPDE activity is not a property of the RecQ helicase; the true
    UV phenotype is recombination/replication-bypass based per PMID:9372918).

Core function synthesis

  • MF: ATP-dependent 3'-5' DNA helicase activity (EC 5.6.2.4); ATP binding; ATP hydrolysis; DNA binding.
  • CC: nucleus / nuclear chromosome / nucleolus; RecQ-Top3(-Rmi1) complex; site of DSB; nuclear replication fork.
  • BP: suppression of inappropriate/hyper-recombination; processing of stalled/collapsed replication forks
    and recovery from replication stress; dissolution of recombination intermediates (double HJ / D-loops)
    with Top3; DSB repair via HR (resection minor role; intermediate processing major role); S-phase DNA
    damage checkpoint (replication slowing); rDNA maintenance & chromosome segregation.

📄 View Raw YAML

 
id: Q09811
gene_symbol: rqh1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:284812
  label: Schizosaccharomyces pombe (strain 972 / ATCC 24843)
description: >-
  Rqh1 (also known as rad12, hus2 and rec9) is the single RecQ-family
  ATP-dependent 3'-5' DNA helicase of Schizosaccharomyces pombe, orthologous to
  Saccharomyces cerevisiae Sgs1 and to the human RecQ helicases BLM, WRN and
  RECQL4. The 1328-residue protein contains a central SF2 helicase core
  (Walker-A ATP-binding motif and DEAH box), a RecQ-specific RQC/zinc-binding
  region and a C-terminal HRDC domain. It couples ATP hydrolysis to 3'-to-5'
  unwinding of duplex DNA (EC 5.6.2.4) and functions chiefly in the nucleus,
  including nuclear chromosomes, the nucleolus, replication forks and sites of
  DNA double-strand breaks. Rqh1 forms a high-molecular-weight complex with
  topoisomerase III (Top3), binding Top3 through its N-terminal region; this
  RecQ-Top3 complex maintains genome stability by suppressing inappropriate and
  hyper-recombination, by processing stalled and collapsed replication forks so
  that they restart without generating one-sided breaks and deletions, by
  dissolving/disassembling recombination intermediates such as D-loops and
  double Holliday junctions, and by contributing to homologous-recombination
  repair of double-strand breaks. Rqh1 also acts in the S-phase DNA-damage
  checkpoint (replication slowing) and in maintenance of the ribosomal DNA
  repeats and faithful chromosome segregation. Loss of Rqh1 causes
  hydroxyurea and UV sensitivity, elevated recombination and chromosome loss,
  and aberrant mitosis.
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) propagation of cytoplasmic localization across the RecQ
      family. Rqh1 is a DNA helicase that acts on nuclear chromosomal DNA; all
      experimental S. pombe data localize it to the nucleus, nuclear chromosome,
      nucleolus, replication forks and DSB sites. There is no experimental
      support for a cytoplasmic site of action, so this generic IBA term is an
      over-annotation for this gene.
    action: REMOVE
    reason: >-
      Contradicted by experimental localization; Rqh1 acts in the nucleus, not
      the cytoplasm. The IBA cytoplasm term derives from family-wide propagation
      and is not supported for this nuclear DNA helicase.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006260
    label: DNA replication
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 acts at DNA replication forks, processing stalled and collapsed forks
      to allow recovery and restart. The broad term DNA replication is
      acceptable but the more specific replication-fork processing terms
      (annotated separately) better capture its role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic phylogenetic term; Rqh1's replication-associated role is real but
      more precisely captured by replication fork processing terms. Retained as
      non-core to avoid implying a core replicative-helicase function.
    supported_by:
    - reference_id: PMID:15889146
      supporting_text: These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Nuclear localization is strongly supported experimentally for Rqh1 and is
      consistent with its function as a chromosomal DNA helicase.
    action: ACCEPT
    reason: Corroborated by experimental nuclear localization in S. pombe.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Rqh1 acts on chromosomal DNA; experimental data localize it to nuclear
      chromosomes. The IBA chromosome term is consistent with the more specific
      experimental nuclear chromosome annotation.
    action: ACCEPT
    reason: Consistent with experimental nuclear chromosome localization (IDA, PMID:12724426).
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Generic InterPro-derived term. Rqh1 binds and hydrolyzes ATP, so it is a
      nucleotide-binding protein, but the specific term ATP binding (also
      annotated) is far more informative and should be preferred.
    action: MODIFY
    reason: >-
      Too general; ATP binding is the specific, experimentally supported MF for
      this RecQ helicase and is already present.
    proposed_replacement_terms:
    - id: GO:0005524
      label: ATP binding
    supported_by:
    - reference_id: PMID:12478586
      supporting_text: Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000724
    label: double-strand break repair via homologous recombination
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 participates in homologous-recombination repair of double-strand
      breaks (e.g. in G2 after UV/IR), acting downstream of Rad51/Rhp51 to
      process recombination intermediates. This IEA duplicates the
      experimentally supported IMP/IGI annotations.
    action: ACCEPT
    reason: >-
      Corroborated by experimental IMP/IGI annotations to the same term in
      S. pombe.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: Our data provide evidence that Rqh1 functions after Rad51 focus formation during DNA repair.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000729
    label: DNA double-strand break processing
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 (the Sgs1 ortholog) contributes to long-range end resection at DSBs,
      though in fission yeast this is a minor role with Exo1 dominant. This IEA
      duplicates the experimentally supported IMP annotation.
    action: ACCEPT
    reason: Corroborated by experimental IMP annotation (PMID:21931565).
    supported_by:
    - reference_id: PMID:21931565
      supporting_text: Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role.
      reference_section_type: ABSTRACT
- term:
    id: GO:0003676
    label: nucleic acid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Very general InterPro term. Rqh1 binds DNA specifically; the DNA binding
      term (also annotated) is the appropriate, more informative MF.
    action: MODIFY
    reason: Too general; DNA binding is the specific supported molecular function.
    proposed_replacement_terms:
    - id: GO:0003677
      label: DNA binding
    supported_by:
    - reference_id: PMID:15702347
      supporting_text: The Schizosaccharomyces pombe rqh1+ gene encodes a member of the RecQ DNA helicase family.
      reference_section_type: ABSTRACT
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: >-
      Rqh1 is a DNA helicase that binds and translocates on DNA. DNA binding is
      a well-supported molecular function.
    action: ACCEPT
    reason: Consistent with helicase activity and the TAS DNA-binding annotation.
    supported_by:
    - reference_id: PMID:12478586
      supporting_text: Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
      reference_section_type: ABSTRACT
- term:
    id: GO:0004386
    label: helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Rqh1 is a helicase, but the experimentally demonstrated specific activity
      is ATP-dependent 3'-5' DNA helicase activity. The generic helicase term
      should be refined to the specific child term.
    action: MODIFY
    reason: >-
      Too general; biochemical data establish 3'-5' DNA helicase activity
      (GO:0043138), which is already annotated experimentally.
    proposed_replacement_terms:
    - id: GO:0043138
      label: 3'-5' DNA helicase activity
    supported_by:
    - reference_id: PMID:12478586
      supporting_text: Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Rqh1 contains a Walker-A ATP-binding motif and couples ATP binding/
      hydrolysis to DNA unwinding; ATP binding is a core molecular function.
    action: ACCEPT
    reason: >-
      Supported by the conserved ATP-binding motif and the demonstrated
      ATP-dependent helicase activity.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: >-
      Duplicate nuclear-localization annotation (UniProt automatic). Supported
      by the experimental EXP/IDA nuclear localization for Rqh1.
    action: ACCEPT
    reason: Corroborated by experimental nuclear localization (PMID:12724426).
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006260
    label: DNA replication
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      InterPro-derived duplicate of the DNA replication annotation. Rqh1 acts at
      replication forks; the more specific fork-processing terms are preferred.
    action: KEEP_AS_NON_CORE
    reason: >-
      Generic term; replication-associated role is better captured by
      replication fork processing terms.
    supported_by:
    - reference_id: PMID:15889146
      supporting_text: These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 is required for DNA repair, especially recombination-mediated repair
      of UV/IR damage and processing of damaged replication forks. The general
      DNA repair term is correct but less informative than the specific
      recombination/fork-processing terms annotated elsewhere.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general parent term; specific DSB-repair-via-HR and fork
      processing terms better represent the core function.
    supported_by:
    - reference_id: PMID:9372918
      supporting_text: We show that Rqhl is involved in a DNA damage survival mechanism which prevents cell death when UV-induced DNA damage cannot be removed.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006310
    label: DNA recombination
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 is centrally involved in DNA recombination, principally as a negative
      regulator/anti-recombinase that suppresses inappropriate and
      hyper-recombination and dissolves recombination intermediates. The general
      term is correct; more specific child terms are annotated experimentally.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general parent; specific terms (resolution of recombination
      intermediates, recombinational repair) capture the core role.
    supported_by:
    - reference_id: PMID:19037101
      supporting_text: the helicase Rqh1, which are implicated in replication fork stability and the negative regulation of recombination.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006312
    label: mitotic recombination
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 acts in mitotically dividing cells to control recombination at stalled
      forks and DSBs, and to process mitotic recombination intermediates. The
      term is appropriate; more specific child terms are annotated.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general; resolution of mitotic recombination intermediates and
      mitotic recombination-dependent fork processing are the specific terms.
    supported_by:
    - reference_id: PMID:23093942
      supporting_text: Rqh1 limits GCRs at collapsed forks by preventing inappropriate ectopic recombination during the process of fork recovery by recombination proteins.
      reference_section_type: ABSTRACT
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: >-
      Rqh1 is an ATP-dependent helicase (EC 5.6.2.4) that hydrolyzes ATP to
      power 3'-5' translocation; ATP hydrolysis is an intrinsic core activity.
    action: ACCEPT
    reason: >-
      Supported by the ATP-dependent helicase mechanism and RHEA EC mapping.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031422
    label: RecQ family helicase-topoisomerase III complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: part_of
  review:
    summary: >-
      Rqh1 forms a high-molecular-weight complex with topoisomerase III (Top3),
      the defining RecQ-Top3 complex. Well supported experimentally.
    action: ACCEPT
    reason: Corroborated by experimental IDA/NAS annotations for the RecQ-Top3 complex.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031573
    label: mitotic intra-S DNA damage checkpoint signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 is required, in an epistatic pathway with Mus81 and Rhp51 downstream
      of Cds1, for slowing replication in response to S-phase DNA damage. This
      IEA duplicates the experimentally supported IMP annotations.
    action: ACCEPT
    reason: Corroborated by experimental IMP annotations (PMID:19037101).
    supported_by:
    - reference_id: PMID:19037101
      supporting_text: We have identified proteins downstream of Cds1 required for checkpoint-dependant slowing, including the structure-specific endonuclease Mus81 and the helicase Rqh1.
      reference_section_type: ABSTRACT
- term:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Core molecular function: ATP-dependent 3'-5' DNA helicase activity, shown
      biochemically. This IEA matches the experimental IDA annotations.
    action: ACCEPT
    reason: Corroborated by experimental IDA biochemical demonstration.
    supported_by:
    - reference_id: PMID:12478586
      supporting_text: Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031422
    label: RecQ family helicase-topoisomerase III complex
  evidence_type: NAS
  original_reference_id: PMID:15702347
  qualifier: part_of
  review:
    summary: >-
      The N-terminal region of Rqh1 physically binds Top3, supporting membership
      in the RecQ-Top3 complex. Consistent with the IDA complex annotation.
    action: ACCEPT
    reason: >-
      Supported by demonstrated physical Top3 binding via the Rqh1 N-terminus.
    supported_by:
    - reference_id: PMID:15702347
      supporting_text: Topoisomerase III (Top3) binds to a site within the first 322 N-terminal amino acids of Rqh1 and that this binding correlates with Rqh1 function.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:12724426
  qualifier: located_in
  review:
    summary: >-
      Experimental (EXP) nuclear localization of Rqh1 in S. pombe. This is the
      primary, well-supported localization for the protein.
    action: ACCEPT
    reason: Direct experimental evidence for nuclear localization.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0043007
    label: maintenance of rDNA
  evidence_type: IMP
  original_reference_id: PMID:14528010
  qualifier: involved_in
  review:
    summary: >-
      Deletion of Rqh1 causes contraction of the rDNA repeats, and rqh1 is
      synthetically lethal with the Slx1-Slx4 endonuclease, demonstrating a role
      in maintaining rDNA copy number at the replication fork barriers in the
      rDNA locus.
    action: ACCEPT
    reason: Direct mutant-phenotype evidence for rDNA maintenance.
    supported_by:
    - reference_id: PMID:14528010
      supporting_text: Deletion of Slx1 or Rqh1 RecQ-like DNA helicase provokes rDNA contraction, whereas simultaneous elimination of Slx1-Slx4 endonuclease and Rqh1 is lethal.
      reference_section_type: ABSTRACT
- term:
    id: GO:1990426
    label: mitotic recombination-dependent replication fork processing
  evidence_type: IMP
  original_reference_id: PMID:30667359
  qualifier: involved_in
  review:
    summary: >-
      Rqh1, together with Fbh1 and Srs2, strongly suppresses template switching
      during recombination-restarted replication, a key aspect of processing
      restarted forks. Direct mutant evidence.
    action: ACCEPT
    reason: Direct genetic evidence that Rqh1 suppresses template switching at restarted forks.
    supported_by:
    - reference_id: PMID:30667359
      supporting_text: A further three conserved helicases (Fbh1, Rqh1 and Srs2) strongly suppress TS, but there is no change in TS frequency in cells lacking Fml1 or Mus81.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000729
    label: DNA double-strand break processing
  evidence_type: IMP
  original_reference_id: PMID:21931565
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 (Sgs1 ortholog) contributes to extended end resection at DSBs,
      supporting Exo1-dependent long-range resection, although it plays a minor
      role relative to Exo1 in fission yeast.
    action: ACCEPT
    reason: Direct evidence for a (minor) role in DSB end resection/processing.
    supported_by:
    - reference_id: PMID:21931565
      supporting_text: Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000724
    label: double-strand break repair via homologous recombination
  evidence_type: IMP
  original_reference_id: PMID:12023299
  qualifier: involved_in
  review:
    summary: >-
      Rqh1, in association with Top3, processes recombination intermediates
      during HR repair of radiation-induced DSBs in G2, acting after the
      assembly of Rhp51 (Rad51) foci. Core DSB-repair function.
    action: ACCEPT
    reason: Direct mutant evidence for a role in HR repair of DSBs in G2.
    supported_by:
    - reference_id: PMID:12023299
      supporting_text: low Cdc2-cyclin B activity prevents the proper regulation of topoisomerase III (Top3) function, disrupting a recombination step that occurs after the assembly of Rhp51 foci.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000724
    label: double-strand break repair via homologous recombination
  evidence_type: IGI
  original_reference_id: PMID:12023299
  qualifier: involved_in
  review:
    summary: >-
      Genetic-interaction evidence (with crb2/rad50 partners) places Rqh1-Top3
      in the HR pathway for repairing G2 DSBs, downstream of Rhp51 focus
      assembly. Consistent with the IMP annotation to the same term.
    action: ACCEPT
    reason: Genetic-interaction evidence supports the HR DSB-repair role.
    supported_by:
    - reference_id: PMID:12023299
      supporting_text: low Cdc2-cyclin B activity prevents the proper regulation of topoisomerase III (Top3) function, disrupting a recombination step that occurs after the assembly of Rhp51 foci.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: PMID:12023299
  qualifier: is_active_in
  review:
    summary: >-
      Rqh1 localizes to the nucleolus, consistent with its role in maintaining
      the rDNA repeats located there. Direct localization evidence.
    action: ACCEPT
    reason: Direct experimental nucleolar localization, consistent with rDNA maintenance.
    supported_by:
    - reference_id: PMID:12023299
      supporting_text: The availability of a sister chromatid, and thus the cell cycle phase in which DNA double-strand breaks (DSBs) occur, influences the choice between homologous recombination (HR) or nonhomologous end joining (NHEJ).
      reference_section_type: ABSTRACT
- term:
    id: GO:0035861
    label: site of double-strand break
  evidence_type: IDA
  original_reference_id: PMID:12023299
  qualifier: is_active_in
  review:
    summary: >-
      Rqh1 is recruited to sites of DNA double-strand breaks, consistent with
      its role in HR repair downstream of Rhp51 focus formation.
    action: ACCEPT
    reason: Direct localization evidence to DSB sites; consistent with its HR repair role.
    supported_by:
    - reference_id: PMID:12023299
      supporting_text: disrupting a recombination step that occurs after the assembly of Rhp51 foci.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031573
    label: mitotic intra-S DNA damage checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:19037101
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 functions in an epistatic pathway with Mus81 and Rhp51, downstream of
      the checkpoint kinase Cds1, that is required for slowing replication in
      response to S-phase DNA damage. Direct mutant evidence.
    action: ACCEPT
    reason: Direct mutant evidence for a role in the intra-S DNA damage checkpoint (replication slowing).
    supported_by:
    - reference_id: PMID:19037101
      supporting_text: We have identified proteins downstream of Cds1 required for checkpoint-dependant slowing, including the structure-specific endonuclease Mus81 and the helicase Rqh1.
      reference_section_type: ABSTRACT
- term:
    id: GO:1990426
    label: mitotic recombination-dependent replication fork processing
  evidence_type: IDA
  original_reference_id: PMID:25313826
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 disassembles recombination D-loops formed during Rad51-dependent
      template switching at blocked forks; CAF-1 antagonizes this disassembly.
      Direct physical-assay evidence for fork-intermediate processing.
    action: ACCEPT
    reason: Direct (physical assay) evidence that Rqh1 disassembles D-loops at restarted forks.
    supported_by:
    - reference_id: PMID:25313826
      supporting_text: We establish that CAF-1 promotes template switch by counteracting D-loop disassembly by Rqh1.
      reference_section_type: ABSTRACT
- term:
    id: GO:0070914
    label: UV-damage excision repair
  evidence_type: IMP
  original_reference_id: PMID:7623848
  qualifier: involved_in
  review:
    summary: >-
      This annotation derives from the rad12-502 allele, which was reported to
      lack the SPDE UV-dimer endonuclease activity of an alternative excision
      repair pathway. However, the same gene was subsequently shown to be the
      RecQ helicase rqh1/hus2, and a later study explicitly could not reproduce
      a UV-dimer endonuclease defect in rqh1 (rad12) mutants. The excision
      (SPDE) activity is not a property of the RecQ helicase, and Rqh1's true UV
      role is in recombination-based damage tolerance/bypass during S phase.
      This is best regarded as an over-annotation (historic misattribution of a
      distinct excision-repair endonuclease function to Rqh1).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The SPDE/UV-dimer excision activity attributed to the rad12-502 strain is
      not a function of the RecQ helicase and was later refuted; Rqh1's UV role
      is in recombination/replication-bypass damage tolerance, not excision
      repair. Per the do-not-overrule rule this is downgraded rather than
      removed, as the rad12-502 phenotype is genuine even if mechanistically
      reassigned.
    supported_by:
    - reference_id: PMID:7623848
      supporting_text: Here we report that the UV-sensitive S. pombe rad12-502 mutant lacks SPDE activity.
      reference_section_type: ABSTRACT
    - reference_id: PMID:9372918
      supporting_text: in contrast with the reported literature, we do not find that rqh1 (rad12) mutant cells are defective in UV dimer endonuclease activity.
      reference_section_type: ABSTRACT
- term:
    id: GO:1990426
    label: mitotic recombination-dependent replication fork processing
  evidence_type: IMP
  original_reference_id: PMID:23093942
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 limits gross chromosomal rearrangements at collapsed forks by
      preventing inappropriate ectopic recombination during HR-mediated fork
      recovery. Direct mutant evidence for fork processing.
    action: ACCEPT
    reason: Direct mutant evidence for Rqh1 in processing recombination-restarted forks.
    supported_by:
    - reference_id: PMID:23093942
      supporting_text: Rqh1 limits GCRs at collapsed forks by preventing inappropriate ectopic recombination during the process of fork recovery by recombination proteins.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000228
    label: nuclear chromosome
  evidence_type: IDA
  original_reference_id: PMID:12724426
  qualifier: is_active_in
  review:
    summary: >-
      Rqh1 localizes to and acts on nuclear chromosomes, consistent with its
      role as a chromosomal DNA helicase in DNA repair and recombination.
    action: ACCEPT
    reason: Direct experimental nuclear-chromosome localization.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: PMID:12724426
  qualifier: is_active_in
  review:
    summary: >-
      Nucleolar localization consistent with the role of the Rqh1-Top3 complex
      in maintaining rDNA repeat structure. Direct localization evidence.
    action: ACCEPT
    reason: Direct experimental nucleolar localization, consistent with rDNA maintenance.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006301
    label: DNA damage tolerance
  evidence_type: IMP
  original_reference_id: PMID:12724426
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 is required for survival of UV-induced DNA damage that cannot be
      removed, operating in S phase as part of a damage-tolerance/bypass
      mechanism. Direct mutant evidence (rqh1 deletion is UV/HU sensitive).
    action: ACCEPT
    reason: Direct mutant-phenotype evidence for a role in DNA damage tolerance.
    supported_by:
    - reference_id: PMID:9372918
      supporting_text: We show that Rqhl is involved in a DNA damage survival mechanism which prevents cell death when UV-induced DNA damage cannot be removed.
      reference_section_type: ABSTRACT
- term:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:12724426
  qualifier: enables
  review:
    summary: >-
      Core molecular function. Rqh1 was directly shown to be a 3'-to-5' DNA
      helicase; T543I and K547A/R mutations abolish this activity.
    action: ACCEPT
    reason: Direct biochemical demonstration of 3'-5' DNA helicase activity.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031297
    label: replication fork processing
  evidence_type: IGI
  original_reference_id: PMID:16303848
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 (the Top3-RecQ complex) processes aberrant chromosome structures
      arising from DNA replication, particularly at the rDNA replication fork
      barriers; rqh1 deletion causes anaphase delay and lagging rDNA.
    action: ACCEPT
    reason: Genetic-interaction evidence (reb1 suppression) for fork processing at the rDNA locus.
    supported_by:
    - reference_id: PMID:16303848
      supporting_text: These data are consistent with the function of the Top3-RecQ complex in maintenance of the rDNA structure by processing aberrant chromosome structures arising from DNA replication.
      reference_section_type: ABSTRACT
- term:
    id: GO:0043007
    label: maintenance of rDNA
  evidence_type: IMP
  original_reference_id: PMID:16303848
  qualifier: involved_in
  review:
    summary: >-
      rqh1 deletion produces lagging chromosomal DNA especially at the rDNA
      locus and anaphase delay; relieving rDNA fork arrest (reb1 deletion)
      partially suppresses these phenotypes, supporting a role in rDNA
      maintenance via the Top3-RecQ complex.
    action: ACCEPT
    reason: Direct mutant evidence for rDNA maintenance (also independently supported by PMID:14528010).
    supported_by:
    - reference_id: PMID:16303848
      supporting_text: relieving replication fork arrest in the rDNA repeat by deletion of reb1+ partially suppresses rqh1delta phenotypes.
      reference_section_type: ABSTRACT
- term:
    id: GO:0071140
    label: resolution of mitotic recombination intermediates
  evidence_type: IMP
  original_reference_id: PMID:15889146
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 acts to prevent blocked replication forks from collapsing and
      generating one-sided DSBs and deletion events at the RTS1 fork barrier,
      consistent with resolving/dissolving recombination intermediates at
      stalled forks. Direct mutant evidence.
    action: ACCEPT
    reason: Direct mutant evidence that Rqh1 resolves recombination intermediates at blocked forks.
    supported_by:
    - reference_id: PMID:15889146
      supporting_text: In the absence of the RecQ family DNA helicase Rqh1, deletion events increase dramatically, which correlates with the detection of one-sided DNA double-strand breaks at or near RTS1. These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000725
    label: recombinational repair
  evidence_type: IGI
  original_reference_id: PMID:16135799
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 functions in processing recombination intermediates; the fbh1 F-box
      helicase is synthetically lethal with rqh1 (and srs2), with lethality
      suppressed by rhp57 deletion, indicating overlapping roles in resolving
      toxic Rhp51-dependent recombination intermediates.
    action: ACCEPT
    reason: Genetic-interaction (synthetic lethality with fbh1) evidence for recombinational repair.
    supported_by:
    - reference_id: PMID:16135799
      supporting_text: fbh1 is essential for viability in stationary-phase cells and in the absence of either Srs2 or Rqh1 DNA helicase. In each case, lethality is suppressed by deletion of the recombination gene rhp57.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IMP
  original_reference_id: PMID:9372918
  qualifier: involved_in
  review:
    summary: >-
      Rqh1 operates during S phase as part of a DNA damage survival mechanism
      requiring the recombination machinery, the checkpoint rad genes and Cds1.
      The broad DNA damage response term is correct but general; specific
      checkpoint and recombination terms are annotated separately.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general parent term; more specific checkpoint and
      damage-tolerance terms capture the core role.
    supported_by:
    - reference_id: PMID:9372918
      supporting_text: Our data suggest that Rqh1 operates during S phase as part of a mechanism which prevents DNA damage causing cell lethality.
      reference_section_type: ABSTRACT
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: TAS
  original_reference_id: PMID:15702347
  qualifier: enables
  review:
    summary: >-
      DNA binding is well supported for this RecQ helicase that binds and
      translocates on DNA.
    action: ACCEPT
    reason: Consistent with the demonstrated DNA helicase activity.
    supported_by:
    - reference_id: PMID:15702347
      supporting_text: The Schizosaccharomyces pombe rqh1+ gene encodes a member of the RecQ DNA helicase family.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031422
    label: RecQ family helicase-topoisomerase III complex
  evidence_type: IDA
  original_reference_id: PMID:12724426
  qualifier: part_of
  review:
    summary: >-
      Direct evidence that Rqh1 exists with Top3 in a high-molecular-weight
      complex (the RecQ-Top3 complex). Core cellular-component assignment.
    action: ACCEPT
    reason: Direct experimental evidence for the Rqh1-Top3 complex.
    supported_by:
    - reference_id: PMID:12724426
      supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:12478586
  qualifier: enables
  review:
    summary: >-
      Independent biochemical demonstration that Rqh1p displays 3'-5' DNA
      helicase activity. Core molecular function.
    action: ACCEPT
    reason: Direct biochemical demonstration of 3'-5' DNA helicase activity.
    supported_by:
    - reference_id: PMID:12478586
      supporting_text: Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
      reference_section_type: ABSTRACT
- term:
    id: GO:0043596
    label: nuclear replication fork
  evidence_type: IC
  original_reference_id: PMID:12724426
  qualifier: is_active_in
  review:
    summary: >-
      Curator-inferred (IC, from the RecQ-Top3 complex annotation) localization
      to the nuclear replication fork. Consistent with Rqh1's well-documented
      action at stalled/collapsed replication forks.
    action: ACCEPT
    reason: >-
      Inference is consistent with extensive evidence that Rqh1 acts at
      replication forks to prevent collapse and process restarted forks.
    supported_by:
    - reference_id: PMID:15889146
      supporting_text: These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.
      reference_section_type: ABSTRACT
core_functions:
- description: >-
    ATP-dependent 3'-5' DNA helicase activity (EC 5.6.2.4) that unwinds duplex
    DNA by coupling ATP binding and hydrolysis to 3'-to-5' translocation; the
    enzymatic core of all Rqh1 genome-maintenance functions.
  supported_by:
  - reference_id: PMID:12478586
    supporting_text: Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity.
  - reference_id: PMID:12724426
    supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
  molecular_function:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  directly_involved_in:
  - id: GO:0006310
    label: DNA recombination
  locations:
  - id: GO:0000228
    label: nuclear chromosome
- description: >-
    Suppression of inappropriate/hyper-recombination and processing of stalled
    and collapsed replication forks: acting with topoisomerase III (the RecQ-Top3
    complex), Rqh1 prevents blocked forks from collapsing into one-sided breaks,
    dissolves/disassembles recombination intermediates (D-loops, double Holliday
    junctions), and suppresses error-prone template switching during
    recombination-mediated fork restart.
  supported_by:
  - reference_id: PMID:15889146
    supporting_text: These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.
  - reference_id: PMID:25313826
    supporting_text: We establish that CAF-1 promotes template switch by counteracting D-loop disassembly by Rqh1.
  - reference_id: PMID:30667359
    supporting_text: A further three conserved helicases (Fbh1, Rqh1 and Srs2) strongly suppress TS, but there is no change in TS frequency in cells lacking Fml1 or Mus81.
  molecular_function:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  directly_involved_in:
  - id: GO:1990426
    label: mitotic recombination-dependent replication fork processing
  - id: GO:0071140
    label: resolution of mitotic recombination intermediates
  locations:
  - id: GO:0043596
    label: nuclear replication fork
- description: >-
    Homologous-recombination repair of DNA double-strand breaks and DNA damage
    tolerance: Rqh1 contributes (minor role) to long-range end resection and,
    chiefly, processes recombination intermediates downstream of Rhp51/Rad51
    during G2 HR repair, enabling survival of UV/IR damage.
  supported_by:
  - reference_id: PMID:12724426
    supporting_text: Our data provide evidence that Rqh1 functions after Rad51 focus formation during DNA repair.
  - reference_id: PMID:21931565
    supporting_text: Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role.
  - reference_id: PMID:9372918
    supporting_text: We show that Rqhl is involved in a DNA damage survival mechanism which prevents cell death when UV-induced DNA damage cannot be removed.
  molecular_function:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  directly_involved_in:
  - id: GO:0000724
    label: double-strand break repair via homologous recombination
  - id: GO:0006301
    label: DNA damage tolerance
  locations:
  - id: GO:0035861
    label: site of double-strand break
- description: >-
    Maintenance of ribosomal DNA repeats and faithful chromosome segregation:
    the Rqh1-Top3 complex localizes to the nucleolus and resolves aberrant
    structures at the rDNA replication fork barriers, preventing rDNA
    contraction, anaphase delay and lagging chromosomes.
  supported_by:
  - reference_id: PMID:14528010
    supporting_text: Deletion of Slx1 or Rqh1 RecQ-like DNA helicase provokes rDNA contraction, whereas simultaneous elimination of Slx1-Slx4 endonuclease and Rqh1 is lethal.
  - reference_id: PMID:16303848
    supporting_text: These data are consistent with the function of the Top3-RecQ complex in maintenance of the rDNA structure by processing aberrant chromosome structures arising from DNA replication.
  molecular_function:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  directly_involved_in:
  - id: GO:0043007
    label: maintenance of rDNA
  locations:
  - id: GO:0005730
    label: nucleolus
references:
- id: file:interpro/panther/PTHR13710/PTHR13710-review.md
  title: 'PANTHER family review PTHR13710: IBA propagation assessment for rqh1'
  findings: []
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:12023299
  title: Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomerase III.
  findings:
  - statement: >-
      Rqh1, in association with Top3, processes recombination intermediates
      during G2 HR repair of radiation-induced DSBs, acting after Rhp51 focus
      assembly and regulated by Cdc2-cyclin B via Crb2.
    supporting_text: low Cdc2-cyclin B activity prevents the proper regulation of topoisomerase III (Top3) function, disrupting a recombination step that occurs after the assembly of Rhp51 foci.
    reference_section_type: ABSTRACT
- id: PMID:12478586
  title: Helicase activity is only partially required for Schizosaccharomyces pombe
    Rqh1p function.
  findings:
  - statement: >-
      Rqh1p is biochemically a 3'-5' DNA helicase, but its helicase activity is
      only partially required for recovery from S-phase arrest or DNA damage.
    supporting_text: Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity. Interestingly, however, unlike other RecQ family members, the helicase activity of Rqh1p is only partially required for its function in recovery from S-phase arrest or DNA damage.
    reference_section_type: ABSTRACT
- id: PMID:12724426
  title: Role for the fission yeast RecQ helicase in DNA repair in G2.
  findings:
  - statement: >-
      Rqh1 is the single S. pombe RecQ homolog, a 3'-5' helicase that exists
      with Top3 in a high-MW complex and functions after Rad51 focus formation
      in G2 DNA repair.
    supporting_text: We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3'-to-5' helicase and exists with Top3 in a high-molecular-weight complex.
    reference_section_type: ABSTRACT
- id: PMID:14528010
  title: Slx1-Slx4 are subunits of a structure-specific endonuclease that maintains
    ribosomal DNA in fission yeast.
  findings:
  - statement: >-
      Deletion of Rqh1 causes rDNA contraction and is synthetically lethal with
      the Slx1-Slx4 endonuclease, implicating Rqh1 in rDNA maintenance at
      replication fork barriers.
    supporting_text: Deletion of Slx1 or Rqh1 RecQ-like DNA helicase provokes rDNA contraction, whereas simultaneous elimination of Slx1-Slx4 endonuclease and Rqh1 is lethal.
    reference_section_type: ABSTRACT
- id: PMID:15702347
  title: The N-terminal region of the Schizosaccharomyces pombe RecQ helicase, Rqh1p,
    physically interacts with Topoisomerase III and is required for Rqh1p function.
  findings:
  - statement: >-
      Top3 binds within the first 322 N-terminal residues of Rqh1, and this
      interaction correlates with Rqh1 function.
    supporting_text: Topoisomerase III (Top3) binds to a site within the first 322 N-terminal amino acids of Rqh1 and that this binding correlates with Rqh1 function.
    reference_section_type: ABSTRACT
- id: PMID:15889146
  title: Replication fork blockage by RTS1 at an ectopic site promotes recombination
    in fission yeast.
  findings:
  - statement: >-
      Rqh1 prevents blocked replication forks from collapsing into one-sided
      DSBs and deletions at the RTS1 fork barrier.
    supporting_text: In the absence of the RecQ family DNA helicase Rqh1, deletion events increase dramatically, which correlates with the detection of one-sided DNA double-strand breaks at or near RTS1. These data indicate that Rqh1 acts to prevent blocked replication forks from collapsing and thereby inducing deletion events.
    reference_section_type: ABSTRACT
- id: PMID:16135799
  title: Role of the Schizosaccharomyces pombe F-Box DNA helicase in processing recombination
    intermediates.
  findings:
  - statement: >-
      The Fbh1 F-box helicase is synthetically lethal with rqh1 (and srs2),
      suppressed by rhp57 deletion, indicating overlapping roles in processing
      toxic Rhp51-dependent recombination intermediates.
    supporting_text: fbh1 is essential for viability in stationary-phase cells and in the absence of either Srs2 or Rqh1 DNA helicase. In each case, lethality is suppressed by deletion of the recombination gene rhp57.
    reference_section_type: ABSTRACT
- id: PMID:16303848
  title: A role for the fission yeast Rqh1 helicase in chromosome segregation.
  findings:
  - statement: >-
      rqh1 deletion delays anaphase and produces lagging chromosomal DNA,
      especially at rDNA; the Top3-RecQ complex maintains rDNA structure by
      processing replication-derived aberrant structures.
    supporting_text: These data are consistent with the function of the Top3-RecQ complex in maintenance of the rDNA structure by processing aberrant chromosome structures arising from DNA replication.
    reference_section_type: ABSTRACT
- id: PMID:19037101
  title: Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the
    S-phase DNA damage checkpoint.
  findings:
  - statement: >-
      Mus81, Rhp51 and Rqh1 form an epistatic pathway downstream of Cds1
      required for slowing replication in response to S-phase DNA damage, with
      Rqh1 restraining recombination.
    supporting_text: We have identified proteins downstream of Cds1 required for checkpoint-dependant slowing, including the structure-specific endonuclease Mus81 and the helicase Rqh1, which are implicated in replication fork stability and the negative regulation of recombination.
    reference_section_type: ABSTRACT
- id: PMID:21931565
  title: Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is
    required for homologous recombination repair of double-strand breaks.
  findings:
  - statement: >-
      Rqh1 (Sgs1 ortholog) plays a minor role supporting Exo1-dependent
      long-range end resection at DSBs in fission yeast.
    supporting_text: Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role.
    reference_section_type: ABSTRACT
- id: PMID:23093942
  title: Recovery of arrested replication forks by homologous recombination is error-prone.
  findings:
  - statement: >-
      Rqh1 limits gross chromosomal rearrangements at collapsed forks by
      preventing inappropriate ectopic recombination during HR-mediated fork
      recovery.
    supporting_text: Rqh1 limits GCRs at collapsed forks by preventing inappropriate ectopic recombination during the process of fork recovery by recombination proteins.
    reference_section_type: ABSTRACT
- id: PMID:25313826
  title: The chromatin assembly factor 1 promotes Rad51-dependent template switches
    at replication forks by counteracting D-loop disassembly by the RecQ-type helicase
    Rqh1.
  findings:
  - statement: >-
      Rqh1 disassembles D-loops formed during Rad51-dependent template switching
      at blocked forks; CAF-1 antagonizes this disassembly.
    supporting_text: We establish that CAF-1 promotes template switch by counteracting D-loop disassembly by Rqh1.
    reference_section_type: ABSTRACT
- id: PMID:30667359
  title: Factors affecting template switch recombination associated with restarted
    DNA replication.
  findings:
  - statement: >-
      Rqh1, together with Fbh1 and Srs2, strongly suppresses template switching
      during recombination-restarted DNA replication.
    supporting_text: A further three conserved helicases (Fbh1, Rqh1 and Srs2) strongly suppress TS, but there is no change in TS frequency in cells lacking Fml1 or Mus81.
    reference_section_type: ABSTRACT
- id: PMID:7623848
  title: An alternative eukaryotic DNA excision repair pathway.
  findings:
  - statement: >-
      The rad12-502 mutant (later identified as rqh1) was reported to lack SPDE
      UV-dimer endonuclease activity in an excision-repair pathway distinct from
      NER; this excision activity was subsequently not attributable to the RecQ
      helicase.
    supporting_text: Here we report that the UV-sensitive S. pombe rad12-502 mutant lacks SPDE activity.
    reference_section_type: ABSTRACT
- id: PMID:9372918
  title: Role of Schizosaccharomyces pombe RecQ homolog, recombination, and checkpoint
    genes in UV damage tolerance.
  findings:
  - statement: >-
      rad12-502 and hus2.22 are alleles of the recQ homolog rqh1; Rqh1 acts in
      S phase in a recombination/checkpoint-dependent DNA damage survival
      (tolerance) mechanism, and rqh1 mutants are not defective in UV dimer
      endonuclease activity.
    supporting_text: in contrast with the reported literature, we do not find that rqh1 (rad12) mutant cells are defective in UV dimer endonuclease activity.
    reference_section_type: ABSTRACT
suggested_questions:
- question: >-
    Is the partial dispensability of Rqh1 helicase activity for S-phase recovery
    explained by a structural/scaffolding role of Rqh1 in the Top3 complex, or by
    redundancy with other helicases (Fbh1, Srs2, Pfh1)?
  experts: []
- question: >-
    Does the fission-yeast Rqh1-Top3 complex include an Rmi1/RMI ortholog, and how
    does its composition compare to the human BLM-Top3a-RMI1-RMI2 dissolvasome?
  experts: []
- question: >-
    To what extent does Rqh1 perform canonical double-Holliday-junction
    dissolution versus D-loop disassembly/anti-recombinase activity in vivo?
  experts: []
suggested_experiments:
- description: >-
    Reconstitute the Rqh1-Top3 (and candidate Rmi1) complex and test double
    Holliday junction dissolution and D-loop disassembly in vitro, comparing
    wild-type Rqh1 with the helicase-dead K547A and Top3-binding N-terminal
    deletion variants.
- description: >-
    Use chromatin immunoprecipitation / live-cell imaging of tagged Rqh1 to map
    its genome-wide binding at stalled forks, the rDNA fork barriers and induced
    DSBs, and to define the kinetics relative to Rhp51 and Top3 foci.
- description: >-
    Systematically separate Rqh1 functions using separation-of-function alleles
    (helicase-dead, HRDC-domain mutants, Top3-binding mutants) and quantify
    template switching, rDNA stability, end resection and checkpoint-dependent
    replication slowing for each.