OpenScientist hypothesis report on Mus81 mitochondrial localization and mtDNA function
PANTHER family review PTHR13451: IBA propagation assessment for mus81
Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotations Inferred by Curator (IC) using at least one Inferred by Sequence Similarity (ISS) annotation to support the inference
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1.
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The FHA1 domain of the replication checkpoint kinase Cds1 interacts with Mus81, and inactivation of mus81 triggers a checkpoint-dependent delay of mitosis, implicating Mus81 in the replication-stress checkpoint and damage tolerance.
"the forkhead-associated-1 (FHA1) protein-docking domain of Cds1 interacts with Mus81, an evolutionarily conserved damage tolerance protein."
The Holliday junction resolvase SpCCE1 prevents mitochondrial DNA aggregation in Schizosaccharomyces pombe.
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SpCCE1/Ydc2 is a dedicated mitochondrial Holliday-junction resolvase whose loss causes aggregated mitochondrial DNA.
"we show by fluorescence microscopy that a SpCCE1-GFP fusion localises exclusively to the mitochondria of S. pombe."
Mus81-Eme1 are essential components of a Holliday junction resolvase.
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Mus81 and Eme1 form a nuclear endonuclease that resolves Holliday junctions into linear duplex products and is required at a late step of meiotic recombination; the meiotic defect is rescued by a bacterial HJ resolvase.
"We report that Mus81 and an associated protein Eme1 are components of an endonuclease that resolves Holliday junctions into linear duplex products."
Human Mus81-associated endonuclease cleaves Holliday junctions in vitro.
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The conserved Mus81-associated endonuclease cleaves Holliday junctions in vitro, resolving them into linear duplexes by cutting strands of like polarity.
"Mus81-associated endonuclease resolves Holliday junctions into linear duplexes by cutting across the junction exclusively on strands of like polarity."
Functional dissection of the Schizosaccharomyces pombe Holliday junction resolvase Ydc2: in vivo role in mitochondrial DNA maintenance.
The endogenous Mus81-Eme1 complex resolves Holliday junctions by a nick and counternick mechanism.
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The nicked Holliday junction is the preferred substrate of endogenous Mus81-Eme1, which resolves HJs by a nick-and-counternick mechanism; HJs accumulate in a pol-alpha mutant lacking Mus81.
"a nicked HJ is the preferred substrate of endogenous and recombinant Mus81-Eme1."
Fission yeast Mus81.Eme1 Holliday junction resolvase is required for meiotic crossing over but not for gene conversion.
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mus81 mutants have normal/elevated gene conversion but 20-100-fold reduced crossing over, genetically separating the two and establishing Mus81 as required for meiotic crossovers.
"Schizosaccharomyces pombe mus81 mutants have normal or elevated frequencies of gene conversion but 20- to 100-fold reduced frequencies of crossing over."
The involvement of Srs2 in post-replication repair and homologous recombination in fission yeast.
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Mus81-Eme1 and Srs2 act in a post-replication-repair sub-pathway for tolerance/repair of UV-induced DNA damage.
"Srs2 and the structure-specific endonuclease Mus81-Eme1 function in a sub-pathway of PRR for the tolerance/repair of UV-induced damage."
Swi5 acts in meiotic DNA joint molecule formation in Schizosaccharomyces pombe.
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Mus81-Eme1 resolves joint molecules such as Holliday junctions; swi5 deletion suppresses the low spore viability of Mus81-Eme1 mutants, situating Mus81 in joint-molecule processing.
"the swi5 deletion strongly suppressed the low viable spore yield of mutants lacking Mus81*Eme1, which resolves joint molecules such as Holliday junctions."
Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress.
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During acute hydroxyurea arrest, Cds1-dependent phosphorylation removes Mus81 from chromatin and prevents cleavage of stalled forks.
"Moreover, Mus81 undergoes extensive Cds1-dependent phosphorylation and dissociates from chromatin in hydroxyurea-arrested cells, thereby preventing it from cleaving stalled replication forks that could lead to fork breakage and chromosomal rearrangement."
ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.
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Genome-wide YFP localization study; source of the high-throughput nuclear and (uncorroborated) mitochondrial localization calls for Mus81.
"we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein."
The novel gene mus7(+) is involved in the repair of replication-associated DNA damage in fission yeast.
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Mus7 acts in the same pathway as Mus81; mus81 (and mus7) deletion severely impairs repair of MMS-induced DSBs, implicating Mus81 in repair of replication-associated DNA damage.
"In Deltamus7 and Deltamus81 cells, the repair of MMS-induced DNA double-strand breaks (DSBs) is severely impaired."
Mus81 cleavage of Holliday junctions: a failsafe for processing meiotic recombination intermediates?
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Active recombinant S. pombe Mus81-Eme1 robustly cleaves intact Holliday junctions as a backup to its primary nicked-HJ activity; in S. pombe most or all crossovers depend on Mus81, and it also acts at stalled/broken forks and interstrand crosslinks in mitosis.
"in the fission yeast Schizosaccharomyces pombe most, if not all, COs depend on Mus81"
Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the S-phase DNA damage checkpoint.
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Mus81 acts downstream of Cds1 in checkpoint-dependent replication slowing, in an epistatic pathway with Rhp51 and Rqh1, contributing to the S-phase DNA damage checkpoint.
"defining an epistatic pathway in which mus81 is epistatic to rhp51 and rhp51 is epistatic to rqh1."
Regulation of Mus81-Eme1 Holliday junction resolvase in response to DNA damage.
Rad51/Dmc1 paralogs and mediators oppose DNA helicases to limit hybrid DNA formation and promote crossovers during meiotic recombination.
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Rad51/Dmc1 paralog/mediator complexes (incl. Swi5-Sfr1) antagonize the Fml1 and Rqh1 helicases to promote Mus81-Eme1-dependent meiotic crossovers.
"play a major role in antagonizing both the FANCM-family DNA helicase/translocase Fml1 and the RecQ-type DNA helicase Rqh1 to limit hybrid DNA formation and promote Mus81-Eme1-dependent COs."
Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication.
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Mus81-Eme1 cleaves stalled forks and recombination intermediates and is required for the spacer-dependent deletions formed during inter-fork strand annealing at replication termination; recombinant Mus81-Eme1 (but not a catalytic-dead mutant) resolves a model IFSA junction in vitro.
"loss of mus81 causes a > 2 fold reduction in SDDs in strains with either a 2 or 5 kb centromere-proximal spacer DNA (Figure 4B), indicating that Mus81-Eme1 specifically promotes SDDs."