Rfc3 is an ATP-binding small subunit shared by replication factor C and alternative RFC complexes. It contributes to ATP-dependent clamp handling on DNA, supports processive DNA replication and repair, and participates in replication and DNA-damage checkpoint signaling through the Rad17-associated machinery. Its principal functions act on nuclear chromatin.
NAS PMID:16040599 Contrasting effects of Elg1-RFC and Ctf18-RFC inactivation i...
ACCEPT
Summary: DNA replication checkpoint signaling is supported.
Reason: Target rfc3-1 mutants are defective in the hydroxyurea-triggered replication checkpoint; the direct genetic study (PMID:10588638) supports the checkpoint function beyond the cited NAS records.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
NAS PMID:20505337 Roles of the checkpoint sensor clamp Rad9-Rad1-Hus1 (911)-co...
ACCEPT
Summary: DNA replication checkpoint signaling is supported.
Reason: Target rfc3-1 mutants are defective in the hydroxyurea-triggered replication checkpoint; the direct genetic study (PMID:10588638) supports the checkpoint function beyond the cited NAS records.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
Reason: Clamp loading and replication/repair require contact with chromatin; retain the curator's IC location inference in the context of the established nuclear RFC machinery.
Reason: DNA association is consistent with the AAA+ clamp-loader architecture and its DNA-dependent function; this broad binding annotation does not assign polymerase chemistry.
Supporting Evidence:
file:SCHPO/rfc3/rfc3-uniprot.txt
DR InterPro; IPR050238; DNA_Rep/Repair_Clamp_Loader.
Processive synthesis occurred in the presence of PCNA, RFC, and Escherichia coli single strand DNA-binding protein (SSB) and required the presence of ATP.
Reason: The contributes_to qualifier correctly expresses an activity of the assembled RFC complex. Rfc3 is one of its small subunits, and RFC supports ATP-dependent processive DNA synthesis (PMID:10748208).
Processive synthesis occurred in the presence of PCNA, RFC, and Escherichia coli single strand DNA-binding protein (SSB) and required the presence of ATP.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
Reason: The sequence carries the annotated P-loop ATP-binding site, and Rfc3 is an AAA+ small subunit of RFC. ATP binding is appropriate to this subunit.
HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...
ACCEPT
Summary: nucleus is supported.
Reason: Nuclear RFC, checkpoint association with Rad17 and chromosomal replication phenotypes support this compartment. Retain the curated localization records without treating the genome-scale abstract as an individual image. The source excerpt records the target HDA/IC annotation, not a reinspection of the individual microscopy image.
Reason: Nuclear RFC, checkpoint association with Rad17 and chromosomal replication phenotypes support this compartment. Retain the curated localization records without treating the genome-scale abstract as an individual image.
Reason: Nuclear RFC, checkpoint association with Rad17 and chromosomal replication phenotypes support this compartment. Retain the curated localization records without treating the genome-scale abstract as an individual image.
NAS PMID:20505337 Roles of the checkpoint sensor clamp Rad9-Rad1-Hus1 (911)-co...
ACCEPT
Summary: nucleus is supported.
Reason: Nuclear RFC, checkpoint association with Rad17 and chromosomal replication phenotypes support this compartment. Retain the curated localization records without treating the genome-scale abstract as an individual image.
Summary: DNA replication factor C complex is supported.
Reason: Rfc3 was cloned as the third RFC subunit and its conditional mutant shows replication defects (PMID:10588638); this independently grounds the complex-membership inference.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
NAS PMID:15952889 Cellular DNA replicases: components and dynamics at the repl...
ACCEPT
Summary: DNA replication factor C complex is supported.
Reason: Rfc3 was cloned as the third RFC subunit and its conditional mutant shows replication defects (PMID:10588638); this independently grounds the complex-membership inference.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...
KEEP AS NON CORE
Summary: cytosol is reviewed in the context of rfc3.
Reason: Retain the genome-scale cytosolic localization observation as non-core. The established mechanism occurs on nuclear DNA; cytosolic detection alone does not establish a second core function. The source excerpt records the target HDA/IC annotation, not a reinspection of the individual microscopy image.
Summary: DNA replication is reviewed in the context of rfc3.
Reason: The broad DNA replication annotation is compatible with the biology, but DNA-templated DNA replication captures the supported rfc3 function more precisely.
Processive synthesis occurred in the presence of PCNA, RFC, and Escherichia coli single strand DNA-binding protein (SSB) and required the presence of ATP.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
NAS PMID:20505337 Roles of the checkpoint sensor clamp Rad9-Rad1-Hus1 (911)-co...
MODIFY
Summary: DNA replication is reviewed in the context of rfc3.
Reason: The broad DNA replication annotation is compatible with the biology, but DNA-templated DNA replication captures the supported rfc3 function more precisely.
Processive synthesis occurred in the presence of PCNA, RFC, and Escherichia coli single strand DNA-binding protein (SSB) and required the presence of ATP.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
Summary: DNA-templated DNA replication is supported.
Reason: Rfc3 conditional mutants show replication defects, and purified S. pombe RFC supports processive Pol delta DNA synthesis. This is clamp-loader participation in replication, not intrinsic DNA polymerase activity.
Processive synthesis occurred in the presence of PCNA, RFC, and Escherichia coli single strand DNA-binding protein (SSB) and required the presence of ATP.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
NAS PMID:15952889 Cellular DNA replicases: components and dynamics at the repl...
ACCEPT
Summary: DNA-templated DNA replication is supported.
Reason: Rfc3 conditional mutants show replication defects, and purified S. pombe RFC supports processive Pol delta DNA synthesis. This is clamp-loader participation in replication, not intrinsic DNA polymerase activity.
Processive synthesis occurred in the presence of PCNA, RFC, and Escherichia coli single strand DNA-binding protein (SSB) and required the presence of ATP.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
Reason: Rfc3 damage sensitivity and checkpoint defects, together with the RFC-dependent reconstituted repair reaction (PMID:10704216), support participation in DNA repair.
A base mispair-containing substrate is repaired in a reaction requiring S. pombe Uve1p, Rad2p, DNA polymerase delta, replication factor C, proliferating cell nuclear antigen, and T4 DNA ligase.
Reason: RFC small subunits are AAA+ ATPases. The annotated nucleotide-binding site and conserved ATP-dependent clamp-loader mechanism support ATP hydrolysis; these annotations do not assert that isolated Rfc3 performs the entire clamp-loading reaction.
Reason: RFC small subunits are AAA+ ATPases. The annotated nucleotide-binding site and conserved ATP-dependent clamp-loader mechanism support ATP hydrolysis; these annotations do not assert that isolated Rfc3 performs the entire clamp-loading reaction.
Association of Rfc3 and Rad17 in vivo and a significant reduction of the phosphorylated form of Chk1 in rfc3-1 cells after treatments with MMS and gamma or UV irradiation suggested that the checkpoint signal emitted by Rfc3 is linked to the downstream checkpoint machinery via Rad17 and Chk1.
Association of Rfc3 and Rad17 in vivo and a significant reduction of the phosphorylated form of Chk1 in rfc3-1 cells after treatments with MMS and gamma or UV irradiation suggested that the checkpoint signal emitted by Rfc3 is linked to the downstream checkpoint machinery via Rad17 and Chk1.
Reason: The small RFC subunits are shared with Ctf18-RFC, a conserved alternative complex discussed and genetically tested in the cited fission-yeast studies. Retain the PAINT and curator NAS inferences at complex-membership level.
Supporting Evidence:
file:SCHPO/rfc3/rfc3-uniprot.txt
DR GO; GO:0031390; C:Ctf18 RFC-like complex; IBA:GO_Central.
Inactivation of Ctf18-RFC by the deletion of ctf18+, dcc1+ or ctf8+ is lethal in an rfc1-44 background showing that full Ctf18-RFC function is required in the absence of fully functional RFC.
NAS PMID:20505337 Roles of the checkpoint sensor clamp Rad9-Rad1-Hus1 (911)-co...
ACCEPT
Summary: Ctf18 RFC-like complex is supported.
Reason: The small RFC subunits are shared with Ctf18-RFC, a conserved alternative complex discussed and genetically tested in the cited fission-yeast studies. Retain the PAINT and curator NAS inferences at complex-membership level.
Supporting Evidence:
file:SCHPO/rfc3/rfc3-uniprot.txt
DR GO; GO:0031390; C:Ctf18 RFC-like complex; IBA:GO_Central.
Inactivation of Ctf18-RFC by the deletion of ctf18+, dcc1+ or ctf8+ is lethal in an rfc1-44 background showing that full Ctf18-RFC function is required in the absence of fully functional RFC.
Reason: Mass spectrometry of purified fission-yeast Elg1-RFC identifies Rfc3 among its five components (PMID:16040599), directly grounding complex membership.
No additional proteins were identified in these purified preparations, strongly suggesting that Elg1–RFC comprises the Elg1, Rfc2, Rfc3, Rfc4 and Rfc5 proteins only.
IDA PMID:16040599 Contrasting effects of Elg1-RFC and Ctf18-RFC inactivation i...
ACCEPT
Summary: Elg1 RFC-like complex is supported.
Reason: Mass spectrometry of purified fission-yeast Elg1-RFC identifies Rfc3 among its five components (PMID:16040599), directly grounding complex membership.
No additional proteins were identified in these purified preparations, strongly suggesting that Elg1–RFC comprises the Elg1, Rfc2, Rfc3, Rfc4 and Rfc5 proteins only.
Reason: Mass spectrometry of purified fission-yeast Elg1-RFC identifies Rfc3 among its five components (PMID:16040599), directly grounding complex membership.
No additional proteins were identified in these purified preparations, strongly suggesting that Elg1–RFC comprises the Elg1, Rfc2, Rfc3, Rfc4 and Rfc5 proteins only.
NAS PMID:16040599 Contrasting effects of Elg1-RFC and Ctf18-RFC inactivation i...
ACCEPT
Summary: Elg1 RFC-like complex is supported.
Reason: Mass spectrometry of purified fission-yeast Elg1-RFC identifies Rfc3 among its five components (PMID:16040599), directly grounding complex membership.
No additional proteins were identified in these purified preparations, strongly suggesting that Elg1–RFC comprises the Elg1, Rfc2, Rfc3, Rfc4 and Rfc5 proteins only.
IC PMID:16040599 Contrasting effects of Elg1-RFC and Ctf18-RFC inactivation i...
ACCEPT
Summary: DNA clamp unloader activity is supported.
Reason: Rfc3 is a shared component of Elg1-RFC, the clamp-unloading complex. The cited 2005 study establishes membership, not an isolated Rfc3 unloading assay; retain the curated IC inference as participation in the complex-level mechanism.
Supporting Evidence:
file:SCHPO/rfc3/rfc3-uniprot.txt
DR GO; GO:0061860; F:DNA clamp unloader activity; IC:PomBase.
No additional proteins were identified in these purified preparations, strongly suggesting that Elg1–RFC comprises the Elg1, Rfc2, Rfc3, Rfc4 and Rfc5 proteins only.
IDA PMID:10704216 In vitro reconstitution of the Schizosaccharomyces pombe alt...
ACCEPT
Summary: UV-damage excision repair is supported.
Reason: The S. pombe alternative-excision-repair reaction requires RFC. Retain PomBase's experimentally curated process assignment; RFC assists repair synthesis and does not itself excise the lesion (PMID:10704216).
A base mispair-containing substrate is repaired in a reaction requiring S. pombe Uve1p, Rad2p, DNA polymerase delta, replication factor C, proliferating cell nuclear antigen, and T4 DNA ligase.
Reason: The S. pombe alternative-excision-repair reaction requires RFC. Retain PomBase's experimentally curated process assignment; RFC assists repair synthesis and does not itself excise the lesion (PMID:10704216).
A base mispair-containing substrate is repaired in a reaction requiring S. pombe Uve1p, Rad2p, DNA polymerase delta, replication factor C, proliferating cell nuclear antigen, and T4 DNA ligase.
GO:1902983 DNA strand elongation involved in mitotic DNA replication
IDA PMID:10748208 Fidelity of eucaryotic DNA polymerase delta holoenzyme from ...
ACCEPT
Summary: DNA strand elongation involved in mitotic DNA replication is supported.
Reason: Purified S. pombe RFC enables processive Pol delta synthesis with PCNA in an ATP-dependent reaction (PMID:10748208). This supports replication-strand elongation through an accessory clamp-loader role.
Processive synthesis occurred in the presence of PCNA, RFC, and Escherichia coli single strand DNA-binding protein (SSB) and required the presence of ATP.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
GO:1902983 DNA strand elongation involved in mitotic DNA replication
IEA GO_REF:0000117
ACCEPT
Summary: DNA strand elongation involved in mitotic DNA replication is supported.
Reason: Purified S. pombe RFC enables processive Pol delta synthesis with PCNA in an ATP-dependent reaction (PMID:10748208). This supports replication-strand elongation through an accessory clamp-loader role.
Processive synthesis occurred in the presence of PCNA, RFC, and Escherichia coli single strand DNA-binding protein (SSB) and required the presence of ATP.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
GO:1903460 mitotic DNA replication leading strand elongation
ISO GO_REF:0000024
ACCEPT
Summary: mitotic DNA replication leading strand elongation is supported.
Reason: The curator-mediated ortholog transfer is consistent with conserved RFC-dependent PCNA loading during replication. It assigns participation in leading-strand elongation, not polymerase catalytic activity.
Processive synthesis occurred in the presence of PCNA, RFC, and Escherichia coli single strand DNA-binding protein (SSB) and required the presence of ATP.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
Core Functions
Contributes to ATP-dependent DNA clamp loading for replication and repair, with related roles in alternative checkpoint and clamp-unloading complexes.
From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Review rationale: The target-specific rfc3 conditional-mutant study establishes DNA replication defects (PMID:10588638), and purified fission-yeast RFC supports processive DNA synthesis (PMID:10748208). Replication is an established function of this clamp-loader subunit. The existing DNA-templated DNA replication and strand-elongation annotations are more specific, making the generic prediction LSP.
Supporting Evidence:
PMID:10588638: "From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor."