The formation of UV-induced chromosome aberrations involves ERCC1 and XPF but not other nucleotide excision repair genes.
ERCC1-XPF, through its role in nucleotide excision repair (NER), is essential for the repair of DNA damage caused by UV light. ERCC1-XPF is also involved in recombinational repair processes distinct from NER. In rodent cells chromosome aberrations are a common consequence of UV irradiation. We have previously shown that ERCC1-deficient cells have a lower ratio of chromatid exchanges to breaks than wild type cells. We have now confirmed this result and have shown that XPF-deficient cells also have a lower ratio than wild type. However, cells deficient in the other NER genes, XPD, XPB and XPG, all have the same ratio of exchanges to breaks as wild type. This implies that ERCC1-XPF, but not other NER proteins, is involved in the formation of UV-induced chromosome aberrations, presumably through the role of ERCC1-XPF in recombinational repair pathways rather than NER. We suggest that ERCC1-XPF may be involved in the bypass/repair of DNA damage in replicating DNA by an exchange mechanism involving single strand annealing between non-homologous chromosomes. This mechanism would rely on the ability of ERCC1-XPF to trim non-homologous 3' tails.
Chipchase
Michael D
MD
Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Melton
David W
DW
D000818:Animals; D016466:CHO Cells / Q000502:physiology / Q000528:radiation effects; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000528:radiation effects*; D006224:Cricetinae; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases; D009154:Mutation; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014466:Ultraviolet Rays; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5
D004265:DNA Helicases; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D011506:Proteins; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C095888:xeroderma pigmentosum group F protein; C072022:XPBC-ERCC-3 protein