Biology:RAD18
 Generic protein structure example |
E3 ubiquitin-protein ligase RAD18 is an enzyme that in humans is encoded by the RAD18 gene.[1][2][3] A knockout in a human colorectal cancer cell line, HCT116, has also been created.[4]
Function
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.[3]
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.[5] RAD18 is also involved in directing repair of DNA double-strand breaks by homologous recombination in post replicative chromatin.[5] RAD18 appears to promote homologous recombinational repair by recruiting the SMC5,SMC6 (SMC5/6) complex to the DNA breaks.[5]
Interactions
RAD18 has been shown to interact with HLTF,[6] UBE2B[1][2] and UBE2A.[1][2]
References
- ↑ 1.0 1.1 1.2 "Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens". Proceedings of the National Academy of Sciences of the United States of America 97 (14): 7927–32. July 2000. doi:10.1073/pnas.97.14.7927. PMID 10884424. Bibcode: 2000PNAS...97.7927T.
- ↑ 2.0 2.1 2.2 "The human RAD18 gene product interacts with HHR6A and HHR6B". Nucleic Acids Research 28 (14): 2847–54. July 2000. doi:10.1093/nar/28.14.2847. PMID 10908344.
- ↑ 3.0 3.1 "Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=56852.
- ↑ "Human RAD18 is involved in S phase-specific single-strand break repair without PCNA monoubiquitination". Nucleic Acids Research 35 (2): e9. 2007-01-01. doi:10.1093/nar/gkl979. PMID 17158148.
- ↑ 5.0 5.1 5.2 "RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin". Nucleic Acids Res 52 (13): 7687–7703. July 2024. doi:10.1093/nar/gkae499. PMID 38884202.
- ↑ "Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination". Proceedings of the National Academy of Sciences of the United States of America 105 (10): 3768–73. March 2008. doi:10.1073/pnas.0800563105. PMID 18316726. Bibcode: 2008PNAS..105.3768U.
Further reading
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "Interaction of HIV-1 integrase with DNA repair protein hRad18". The Journal of Biological Chemistry 277 (30): 27489–93. July 2002. doi:10.1074/jbc.M203061200. PMID 12016221.
- "Early immobilization of nuclease FEN1 and accumulation of hRAD18 protein at stalled DNA replication forks in mammalian cells". Doklady Biochemistry and Biophysics 389 (1–6): 122–5. 2004. doi:10.1023/A:1023696425171. PMID 12856420.
- "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America 101 (33): 12130–5. August 2004. doi:10.1073/pnas.0404720101. PMID 15302935. Bibcode: 2004PNAS..10112130B.
- "Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination". The EMBO Journal 23 (19): 3886–96. October 2004. doi:10.1038/sj.emboj.7600383. PMID 15359278.
- "DNA damage-induced accumulation of Rad18 protein at stalled replication forks in mammalian cells involves upstream protein phosphorylation". Biochemical and Biophysical Research Communications 323 (3): 831–7. October 2004. doi:10.1016/j.bbrc.2004.08.165. PMID 15381075. Bibcode: 2004BBRC..323..831N.
- "Differential regulation of Rad18 through Rad6-dependent mono- and polyubiquitination". The Journal of Biological Chemistry 280 (1): 515–24. January 2005. doi:10.1074/jbc.M409219200. PMID 15509568.
- "Regulated expression and dynamic changes in subnuclear localization of mammalian Rad18 under normal and genotoxic conditions". Genes to Cells 10 (8): 753–62. August 2005. doi:10.1111/j.1365-2443.2005.00874.x. PMID 16098139.
- "Phosphoproteome analysis of the human mitotic spindle". Proceedings of the National Academy of Sciences of the United States of America 103 (14): 5391–6. April 2006. doi:10.1073/pnas.0507066103. PMID 16565220. Bibcode: 2006PNAS..103.5391N.
- "Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase checkpoint-mediated arrest". Molecular and Cellular Biology 26 (9): 3527–40. May 2006. doi:10.1128/MCB.26.9.3527-3540.2006. PMID 16611994.
- "Effect of DNA repair protein Rad18 on viral infection". PLOS Pathogens 2 (5): e40. May 2006. doi:10.1371/journal.ppat.0020040. PMID 16710452.
- "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". Genes to Cells 11 (7): 731–44. July 2006. doi:10.1111/j.1365-2443.2006.00974.x. PMID 16824193.
- "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology 24 (10): 1285–92. October 2006. doi:10.1038/nbt1240. PMID 16964243.
- "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. November 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
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