RAD18

The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through interaction with Rad6, which is a ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved ring finger motif. Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens.

RAD18 is an E3 ubiquitin ligase that enables movement of ubiquitin from a ubiquitin carrier to another protein (the substrate). One activity of RAD18 is to prevent replication fork collapse by promoting DNA translesion synthesis and template switching.{{cite journal |vauthors=Palek M, Palkova N, Kleiblova P, Kleibl Z, Macurek L |title=RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin |journal=Nucleic Acids Res |volume=52 |issue=13 |pages=7687–7703 |date=July 2024 |pmid=38884202 |doi=10.1093/nar/gkae499 |pmc=11260465 |url=}} RAD18 is also involved in directing repair of DNA double-strand breaks by homologous recombination in post replicative chromatin. RAD18 appears to promote homologous recombinational repair by recruiting the SMC5,SMC6 (SMC5/6) complex to the DNA breaks.

RAD18 has been shown to interact with HLTF,{{cite journal | vauthors = Unk I, Hajdú I, Fátyol K, Hurwitz J, Yoon JH, Prakash L, Prakash S, Haracska L | title = Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 10 | pages = 3768–73 | date = March 2008 | pmid = 18316726 | pmc = 2268824 | doi = 10.1073/pnas.0800563105 | bibcode = 2008PNAS..105.3768U | doi-access = free }} UBE2B and UBE2A.

{{reflist}}

{{refbegin|32em}}

• {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
• {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
• {{cite journal | vauthors = Mulder LC, Chakrabarti LA, Muesing MA | title = Interaction of HIV-1 integrase with DNA repair protein hRad18 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 30 | pages = 27489–93 | date = July 2002 | pmid = 12016221 | doi = 10.1074/jbc.M203061200 | doi-access = free }}
• {{cite journal | vauthors = Nikiforov AA, Sasina LK, Svetlova MP, Solovjeva LV, Oei SL, Bradbury EM, Tomilin NV | title = Early immobilization of nuclease FEN1 and accumulation of hRAD18 protein at stalled DNA replication forks in mammalian cells | journal = Doklady Biochemistry and Biophysics | volume = 389 | pages = 122–5 | year = 2004 | pmid = 12856420 | doi = 10.1023/A:1023696425171 | s2cid = 2646911 }}
• {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = August 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 | bibcode = 2004PNAS..10112130B | doi-access = free }}
• {{cite journal | vauthors = Watanabe K, Tateishi S, Kawasuji M, Tsurimoto T, Inoue H, Yamaizumi M | title = Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination | journal = The EMBO Journal | volume = 23 | issue = 19 | pages = 3886–96 | date = October 2004 | pmid = 15359278 | pmc = 522788 | doi = 10.1038/sj.emboj.7600383 }}
• {{cite journal | vauthors = Nikiforov A, Svetlova M, Solovjeva L, Sasina L, Siino J, Nazarov I, Bradbury M, Tomilin N | title = DNA damage-induced accumulation of Rad18 protein at stalled replication forks in mammalian cells involves upstream protein phosphorylation | journal = Biochemical and Biophysical Research Communications | volume = 323 | issue = 3 | pages = 831–7 | date = October 2004 | pmid = 15381075 | doi = 10.1016/j.bbrc.2004.08.165 }}
• {{cite journal | vauthors = Miyase S, Tateishi S, Watanabe K, Tomita K, Suzuki K, Inoue H, Yamaizumi M | title = Differential regulation of Rad18 through Rad6-dependent mono- and polyubiquitination | journal = The Journal of Biological Chemistry | volume = 280 | issue = 1 | pages = 515–24 | date = January 2005 | pmid = 15509568 | doi = 10.1074/jbc.M409219200 | doi-access = free }}
• {{cite journal | vauthors = Masuyama S, Tateishi S, Yomogida K, Nishimune Y, Suzuki K, Sakuraba Y, Inoue H, Ogawa M, Yamaizumi M | title = Regulated expression and dynamic changes in subnuclear localization of mammalian Rad18 under normal and genotoxic conditions | journal = Genes to Cells | volume = 10 | issue = 8 | pages = 753–62 | date = August 2005 | pmid = 16098139 | doi = 10.1111/j.1365-2443.2005.00874.x | s2cid = 41733250 | doi-access = free }}
• {{cite journal | vauthors = Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R | title = Phosphoproteome analysis of the human mitotic spindle | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 14 | pages = 5391–6 | date = April 2006 | pmid = 16565220 | pmc = 1459365 | doi = 10.1073/pnas.0507066103 | bibcode = 2006PNAS..103.5391N | doi-access = free }}
• {{cite journal | vauthors = Bi X, Barkley LR, Slater DM, Tateishi S, Yamaizumi M, Ohmori H, Vaziri C | title = Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase checkpoint-mediated arrest | journal = Molecular and Cellular Biology | volume = 26 | issue = 9 | pages = 3527–40 | date = May 2006 | pmid = 16611994 | pmc = 1447421 | doi = 10.1128/MCB.26.9.3527-3540.2006 }}
• {{cite journal | vauthors = Lloyd AG, Tateishi S, Bieniasz PD, Muesing MA, Yamaizumi M, Mulder LC | title = Effect of DNA repair protein Rad18 on viral infection | journal = PLOS Pathogens | volume = 2 | issue = 5 | pages = e40 | date = May 2006 | pmid = 16710452 | pmc = 1463017 | doi = 10.1371/journal.ppat.0020040 | doi-access = free }}
• {{cite journal | vauthors = Yuasa MS, Masutani C, Hirano A, Cohn MA, Yamaizumi M, Nakatani Y, Hanaoka F | title = A human DNA polymerase eta complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest | journal = Genes to Cells | volume = 11 | issue = 7 | pages = 731–44 | date = July 2006 | pmid = 16824193 | doi = 10.1111/j.1365-2443.2006.00974.x | s2cid = 32695133 | doi-access = free }}
• {{cite journal | vauthors = Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP | title = A probability-based approach for high-throughput protein phosphorylation analysis and site localization | journal = Nature Biotechnology | volume = 24 | issue = 10 | pages = 1285–92 | date = October 2006 | pmid = 16964243 | doi = 10.1038/nbt1240 | s2cid = 14294292 }}
• {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = November 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 | s2cid = 7827573 | doi-access = free }}

{{refend}}

Category:Genes mutated in mice

Category:DNA repair