| Structural highlights
Function
[RAD5_YEAST] Probable helicase, member of the UBC2/RAD6 epistasis group. Functions with the DNA repair protein RAD18 in error-free postreplication DNA repair. Involved in the maintenance of wild-type rates of instability of simple repetitive sequences such as poly(GT) repeats. Seems to be involved in maintaining a balance which acts in favor of error-prone non-homologous joining during DNA double-strand breaks repairs. Recruits the UBC13-MMS2 dimer to chromatin for DNA repair.[1] [2] [3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
DNA damage tolerance (DDT) is responsible for genomic stability and cell viability by bypassing the replication block. In Saccharomyces cerevisiae DDT employs two parallel branch pathways to bypass the DNA lesion, namely translesion DNA synthesis (TLS) and error-free lesion bypass, which are mediated by sequential modifications of PCNA. Rad5 has been placed in the error-free branch of DDT because it contains an E3 ligase domain required for PCNA polyubiquitination. Rad5 is a multi-functional protein and may also play a role in TLS, since it interacts with the TLS polymerase Rev1. In this study we mapped the Rev1-interaction domain in Rad5 to the amino acid resolution and demonstrated that Rad5 is indeed involved in TLS possibly through recruitment of Rev1. Genetic analyses show that the dual functions of Rad5 can be separated and reconstituted. Crystal structure analysis of the Rad5-Rev1 interaction reveals a consensus RFF motif in the Rad5 N-terminus that binds to a hydrophobic pocket within the C-terminal domain of Rev1 that is highly conserved in eukaryotes. This study indicates that Rad5 plays a critical role in pathway choice between TLS and error-free DDT.
Involvement of budding yeast Rad5 in translesion DNA synthesis through physical interaction with Rev1.,Xu X, Lin A, Zhou C, Blackwell SR, Zhang Y, Wang Z, Feng Q, Guan R, Hanna MD, Chen Z, Xiao W Nucleic Acids Res. 2016 Jun 20;44(11):5231-45. doi: 10.1093/nar/gkw183. Epub 2016, Mar 21. PMID:27001510[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ulrich HD, Jentsch S. Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J. 2000 Jul 3;19(13):3388-97. PMID:10880451 doi:http://dx.doi.org/10.1093/emboj/19.13.3388
- ↑ Xiao W, Chow BL, Broomfield S, Hanna M. The Saccharomyces cerevisiae RAD6 group is composed of an error-prone and two error-free postreplication repair pathways. Genetics. 2000 Aug;155(4):1633-41. PMID:10924462
- ↑ Torres-Ramos CA, Prakash S, Prakash L. Requirement of RAD5 and MMS2 for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol Cell Biol. 2002 Apr;22(7):2419-26. PMID:11884624
- ↑ Hoege C, Pfander B, Moldovan GL, Pyrowolakis G, Jentsch S. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature. 2002 Sep 12;419(6903):135-41. PMID:12226657 doi:10.1038/nature00991
- ↑ Ulrich HD. Protein-protein interactions within an E2-RING finger complex. Implications for ubiquitin-dependent DNA damage repair. J Biol Chem. 2003 Feb 28;278(9):7051-8. doi: 10.1074/jbc.M212195200. Epub 2002, Dec 19. PMID:12496280 doi:http://dx.doi.org/10.1074/jbc.M212195200
- ↑ Johnson RE, Henderson ST, Petes TD, Prakash S, Bankmann M, Prakash L. Saccharomyces cerevisiae RAD5-encoded DNA repair protein contains DNA helicase and zinc-binding sequence motifs and affects the stability of simple repetitive sequences in the genome. Mol Cell Biol. 1992 Sep;12(9):3807-18. PMID:1324406
- ↑ Chen S, Davies AA, Sagan D, Ulrich HD. The RING finger ATPase Rad5p of Saccharomyces cerevisiae contributes to DNA double-strand break repair in a ubiquitin-independent manner. Nucleic Acids Res. 2005 Oct 13;33(18):5878-86. Print 2005. PMID:16224103 doi:http://dx.doi.org/33/18/5878
- ↑ Ahne F, Jha B, Eckardt-Schupp F. The RAD5 gene product is involved in the avoidance of non-homologous end-joining of DNA double strand breaks in the yeast Saccharomyces cerevisiae. Nucleic Acids Res. 1997 Feb 15;25(4):743-9. PMID:9016623
- ↑ Xu X, Lin A, Zhou C, Blackwell SR, Zhang Y, Wang Z, Feng Q, Guan R, Hanna MD, Chen Z, Xiao W. Involvement of budding yeast Rad5 in translesion DNA synthesis through physical interaction with Rev1. Nucleic Acids Res. 2016 Jun 20;44(11):5231-45. doi: 10.1093/nar/gkw183. Epub 2016, Mar 21. PMID:27001510 doi:http://dx.doi.org/10.1093/nar/gkw183
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