Highly elevated ultraviolet-induced mutation frequency in isolated Chinese hamster cell lines defective in nucleotide excision repair and mismatch repair proteins.
We have isolated N-methyl-N'-nitro-N-nitrosoguanidine-resistant cell lines from 43-3B Chinese hamster ovary cells, which are deficient in the ERCC1 gene involved in nucleotide excision repair. By Western blotting analysis, we found cell lines that are deficient or decreased in the amount of MSH6, or PMS2, or MSH2 proteins. Cell extracts of these cell lines show reduced efficiency of G:T mismatch repair activity. Compared with 43-3B, these cell lines exhibit highly elevated UV-induced mutation rates, indicating that mammalian mismatch repair can suppress UV-induced mutagenesis and may play a role in the fidelity of DNA replication at the sites of UV damage.
Nara
K
K
Department of Molecular Genetics, Institute of Development, Aging and Cancer, Medical Faculty, Tohoku University, Sendai, Japan.
Nagashima
F
F
Yasui
A
A
D000251:Adenosine Triphosphatases; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D020137:Base Pair Mismatch / Q000502:physiology*; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002999:Clone Cells; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D004351:Drug Resistance; D004720:Endonucleases; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D000070976:Mismatch Repair Endonuclease PMS2; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014466:Ultraviolet Rays
D000477:Alkylating Agents; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C098790:MSH6 protein, S cerevisiae; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D008769:Methylnitronitrosoguanidine; C071447:ERCC1 protein, human; D004720:Endonucleases; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes