Specificity of mutations in the PMS2-deficient human tumor cell line HEC-1-A.
The spectrum of mutations was determined at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in the human uterine tumor cell line HEC-1-A which is defective in the mismatch repair gene hPMS2. The mutation frequency at the hprt locus in HEC-1-A was about two orders higher than that in wild type repair-proficient cells. The fifty-eight mutations detected were exclusively point mutations, with frameshifts of one base deletion/addition predominating (66%) the remaining were base substitutions. All the frameshift mutations occurred at sites of monotonous repeating sequences, including six consecutive guanine bases site which was the hot spot for the addition of one G that contributed 60% of the total mutations. Although the observed specificity of mutations in HEC-1-A apparently resembled that of the hMLH1-deficient cell line HCT116 [Ohzeki, S., Tachibana, A., Tatsumi, T., Kato, T., 1997. Spectra of spontaneous mutations at the hprt locus in colorectal carcinoma cell lines defective in mismatch repair. Carcinogenesis, 18, 1127-1133.], the pronounced increase of +/-1 bp frameshifts and the reduced incidence of C-->T transitions at the CpG site suggest that the hPMS2 gene product may have an additional function in the mismatch repair process independent of it's role in the hMutLalpha heterodimer.
Kato
T
T
Radiation Biology Center, Kyoto University, Kyoto 606, Japan. kato@house.rbc.kyo
Yatagai
F
F
Glickman
B W
BW
Tachibana
A
A
Ikenaga
M
M
D000251:Adenosine Triphosphatases; D002277:Carcinoma / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D000070976:Mismatch Repair Endonuclease PMS2; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D011506:Proteins; D007041:Hypoxanthine Phosphoribosyltransferase; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes