Sensitivity of group F xeroderma pigmentosum cells to UV and mitomycin C relative to levels of XPF and ERCC1 overexpression.
The XPF and ERCC1 proteins form a tight complex and function as an endonuclease to incise on the 5'-side of pyrimidine dimers in DNA. Levels of both proteins are extremely low in group F xeroderma pigmentosum (XP-F) cells. We transfected XP-F cells with the plasmids expressing XPF or ERCC1 and examined levels of both proteins in the cells. Although XP-F cells are sensitive to UV and mitomycin C (MMC), cells overexpressing XPF expressed ERCC1 as well and resistance to UV and MMC was restored to the normal level. In contrast, cells overexpressing ERCC1 did not express XPF and were still sensitive to UV and MMC. These results indicate that both the XPF and ERCC1 proteins are required to repair UV- and MMC-induced DNA damage. Even though a high level of ERCC1, which has been presumed to be a catalytic subunit of the endonuclease, is stably present in XP-F cells, ERCC1 protein alone cannot carry out excision repair completely.
Yagi
T
T
Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Japan. c51845@sakura.kudpc.kyoto-u.ac.jp
Katsuya
A
A
Koyano
A
A
Takebe
H
H
D002999:Clone Cells; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004720:Endonucleases; D005260:Female; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014162:Transfection; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy
D004268:DNA-Binding Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011506:Proteins; C095888:xeroderma pigmentosum group F protein; D016685:Mitomycin; C071447:ERCC1 protein, human; D004720:Endonucleases