Spontaneous mutations at aprt locus in a mammalian cell line defective in mismatch recognition.
Clone B is a CHO cell line that shows a moderate mutator phenotype as a consequence of a defect in mismatch recognition. To identify the classes of mutation that accumulate spontaneously in a functional gene, we isolated and sequenced 54 clone B spontaneous mutants at the adenine phosphoribosyltransferase gene. This spectrum was compared to 42 mutants collected in the parental cells. Rates of AT-->TA transversions and frameshifts were strikingly increased in clone B (almost eight- and sixfold, respectively). Minor increases were also observed for GC-->TA transversions and GC-->AT transition rates. Frameshifts occurred in repeated sequences, and a large proportion were losses of 2 bases occurring in dinucleotide runs of a type similar to microsatellite sequences. AT-->TA transversions clustered in regions of secondary structure and their formation might be explained by slippage-mediated mechanisms. These data indicate that an important function of mismatch recognition is in repair of extrahelical bases generated by misalignment during DNA replication.
Hess
P
P
Istituto Superiore di Sanità, Section of Chemical Carcinogenesis, Rome, Italy.
Aquilina
G
G
Dogliotti
E
E
Bignami
M
M
D000228:Adenine Phosphoribosyltransferase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004261:DNA Replication; D016368:Frameshift Mutation; D008969:Molecular Sequence Data; D009154:Mutation; D009692:Nucleic Acid Heteroduplexes
D009692:Nucleic Acid Heteroduplexes; D004247:DNA; D000228:Adenine Phosphoribosyltransferase