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Nucleotide Excision Repair
Last Updated: 2019-08-16
In order to pass genetic information from one generation to the next, all organisms must accurately replicate their genomes during each cell division. This includes the nuclear genome and mitochondrial and chloroplast genomes. These are normally replicated with high fidelity that is achieved through the action of accurate DNA repair. Nucleotide Excision Repair is one os several mechanisms of DNA repair. Nucleotide excision repair (NER) operates on base damage caused by exogenous agents (such as mutagenic and carcinogenic chemicals and photoproducts generated by sunlight exposure) that cause alterations in the chemistry and structure of the DNA duplex . Such damage is recognized by a protein called XPC, which is stably bound to another protein called HHRAD23B (R23). The binding of the XPC–HHRAD23 heterodimeric subcomplex is followed by the binding of several other proteins (XPA, RPA, TFIIH and XPG). Of these, XPA and RPA are believed to facilitate specific recognition of base damage. TFIIH is a subcomplex of the RNA polymerase II transcription initiation machinery which also operates during NER. It consists of six subunits and contains two DNA helicase activities (XPB and XPD) that unwind the DNA duplex in the immediate vicinity of the base damage. This local denaturation generates a bubble in the DNA, the ends of which comprise junctions between duplex and single-stranded DNA. The subsequent binding of the ERCC1–XPF heterodimeric subcomplex generates a completely assembled NER multiprotein complex. XPG is a duplex/single-stranded DNA endonuclease that cuts the damaged strand at such junctions 3’ to the site of base damage. Conversely, the ERCC1–XPF heterodimeric protein is a duplex/single-stranded DNA endonuclease that cuts the damaged strand at such junctions 5’ to the site of base damage. This bimodal incision generates an oligonucleotide fragment 27–30 nucleotides in length which includes the damaged base. This fragment is excised from the genome, concomitant with restoring the potential 27–30 nucleotide gap by repair synthesis. Repair synthesis requires DNA polymerases or , as well as the accessory replication proteins PCNA, RPA and RFC. The covalent integrity of the damaged strand is then restored by DNA ligase. Collectively, these biochemical events return the damaged DNA to its native chemistry and configuration. ERCC1, excision repair cross-complementing 1; PCNA, proliferating cell nuclear antigen; POL, polymerase; RFC, replication factor C; RPA, replication protein A; TFIIH, transcription factor IIH; XP, xeroderma pigmentosum.
Nucleotide Excision Repair References
Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012-8. doi: 10.1126/science.282.5396.2012.Pubmed: 9851916
Barber LJ, Youds JL, Ward JD, McIlwraith MJ, O'Neil NJ, Petalcorin MI, Martin JS, Collis SJ, Cantor SB, Auclair M, Tissenbaum H, West SC, Rose AM, Boulton SJ: RTEL1 maintains genomic stability by suppressing homologous recombination. Cell. 2008 Oct 17;135(2):261-71. doi: 10.1016/j.cell.2008.08.016.Pubmed: 18957201
Youds JL, Mets DG, McIlwraith MJ, Martin JS, Ward JD, ONeil NJ, Rose AM, West SC, Meyer BJ, Boulton SJ: RTEL-1 enforces meiotic crossover interference and homeostasis. Science. 2010 Mar 5;327(5970):1254-8. doi: 10.1126/science.1183112.Pubmed: 20203049
Bird DM, Riddle DL: Molecular cloning and sequencing of ama-1, the gene encoding the largest subunit of Caenorhabditis elegans RNA polymerase II. Mol Cell Biol. 1989 Oct;9(10):4119-30. doi: 10.1128/mcb.9.10.4119.Pubmed: 2586513
Wallenfang MR, Seydoux G: cdk-7 Is required for mRNA transcription and cell cycle progression in Caenorhabditis elegans embryos. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5527-32. doi: 10.1073/pnas.082618399.Pubmed: 11960010
This pathway was propagated using PathWhiz - Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000478
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