Table 1.
Proteins involved in DNA damage tolerance through homologous recombinationa
| Yeast | Humans | Functions |
|---|---|---|
| Rad51 | Rad51 | Forms a nucleofilament on ssDNA that is essential for homology search, ssDNA annealing, and strand exchange |
| Rad52 | Rad52; BRCA2 | Mediate the assembly of Rad51 on RPA-coated ssDNA; promote ssDNA annealing and D-loop formation |
| RPA | RPA | ssDNA binding protein; competes with Rad51 for ssDNA binding; modulates DNA damage repair/tolerance and checkpoint activation |
| Rad55/Rad57 | XRCC3/RAD51C/ XRCC2/RAD51B/RAD51D | Rad51 paralogs; counteract Srs2 activity by stabilizing the Rad51 nucleofilament; facilitate Rad51-mediated strand exchange |
| Csm2/Psy3/ Shu1/Shu2/ | RAD51D/SWS1 | Like Rad55/Rad57, the yeast Shu complex counteracts Srs2 activities but its function is restricted to replicative non-DSB DNA lesions |
| Rad54 | Rad54 | Stabilizes Rad51 nucleofilaments and stimulates Rad51-dependent DNA annealing; dissociates Rad51 from dsDNA via its translocase activity; remodels chromatin |
| Mre11/Rad50/Xrs2 | Mre11/Rad50/Nbs1 | Heterotrimeric complex with ATPase and nuclease activities; regulates ssDNA resection; structural role bridging sister chromatids; Nbs1 has an additional role in recruiting Rad18 to UV-induced lesions |
| Sae2 | CtP1; BRCA1 | Initiate DNA resection by counteracting the inhibitory activities of the Ku/DNA-PK complex and Rad9/53BP1; BRCA1 facilitates recruitment of Rad18, HLTF, and Pol η to replicative lesions |
| Exo1 | Exo1 | Structure-specific nuclease involved in processing stalled forks |
| Sgs1/ Top3/Rmi1 | BLM; WRN; SMARCAL1; BLM/TopoIIIα/ Rmi1/Rmi2 | Sgs1, BLM, WRN, and SMARCAL1 are DNA helicases with fork reversal and HJ migration activities; the helicase and topoisomerase activities of Sgs1/BLM and topoisomerase III are required together with Rmi1/Rmi2 for HJ dissolution |
| Ubc9/Mms21 | Ubc9/Mms21 | E2 conjugase (Ubc9) and E3 ligase (Mms21) sumoylation complex that acts in concert with Sgs1/Top3/Rmi1 to resolve HJs, probably by sumoylation of the Smc5-6 complex |
| Smc5–6 | Smc5/Smc6 | Multisubunit complex involved in DSB repair and fork restart by HR and in resolution of MMS-induced SCJs |
| Rad17/Mec3/Ddc1 | Rad9/Rad1/Hus1 | PCNA-like checkpoint clamp; required for full checkpoint activation, and MMS-induced HR in a checkpoint-independent manner |
| Pol δ | Pol δ | Lagging strand synthesis DNA polymerase |
| Pol η | Pol η | TLS polymerase; co-localizes with Rad51 foci after UV irradiation in human cells |
| PCNA | PCNA | Replication processivity factor; loaded by RFC and interacts with DNA polymerases and DNA repair factors via post-transcriptional modifications that control DNA replication and damage tolerance |
| Rad6/ Rad18 | HHR6A; HHR6B/Rad18 | E2 conjugase (Rad6; HHR6A; HHR6B) and E3 ligase (Rad18) ubiquitination complex that monoubiquitinates PCNA to promote TLS; recruited to replicative DNA lesions through the ssDNA binding activity of Rad18 |
| Mms2/Ubc13/ Rad5 | Mms2/Ubc13/HLTF; SHPRH | E2 conjugase (Mms2/Ubc13) and E3 ligase (Rad5, HLTF, SHPRH) ubiquitination complex that extends PCNA K164 ubiquitination with a K63-linked ubiquitin chain to promote template switch; Rad5 and HLTF have also dsDNA translocase activity that promotes fork reversal |
| Mgs1 | WRNIP1; ZRAMB3/AH2 | DNA helicases that bind to ubiquitinated PCNA; Mgs1 destabilizes the interactions between PCNA and Pol δ; ZRAMB3/AH2 has fork reversal and cleavage activity |
| Ubc9/Siz1 | Ubc9/RFC | E2 conjugase (Ubc9) and E3 ligase (Siz1) sumoylation complex that sumoylates PCNA to recruit Srs2; Ubc9 and RFC are sufficient for human PCNA sumoylation in vitro |
| Srs2 | PARI | Sumoylated PCNA interacting DNA helicase that inhibits the salvage HR pathway during S phase by interfering with the formation of ssDNA/Rad51 nucleofilaments and inhibiting DNA repair synthesis |
| Elg1 | ATAD5 | RFC-like clamp loader; interacts with sumoylated PCNA to unload it from chromatin; ATAD5 recruits the ubiquitinating enzyme USP1 |
| Hmo1 | HMGB | Chromatin structural DNA bending protein that binds cruciform structures and promotes Rad51-, Rad5-dependent SCJ formation and prevents function of the salvage HR pathway during S phase |
| Ino80 | Ino80 | ATP-dependent chromatin remodeling complex; facilitates the recruitment of Rad51 and Rad18 to MMS-stressed forks |
aOnly proteins (and their orthologs or functional counterparts) and functions mentioned in the text are shown. Abbreviations: DSB, double-strand break; HJ, Holliday junction; HR, homologous recombination; MMS, methylmethane sulfonate; PCNA, proliferating cell nuclear antigen; RFC, replication factor C; SCJ, sister-chromatid junction; TLS, translesion synthesis.