Association of mutator activity with UV sensitivity in an aphidicolin-resistant mutant of Chinese hamster V79 cells

Abstract

The spontaneous mutation rates of an ultraviolet light (UV)-sensitive aphidicolin-resistant mutant (aphr-4-2) and its revertants have been determined by 2 techniques. By using the fluctuation analysis, the mutant and its thymidine (TdR)-prototrophic 'revertant' were found to exhibit elevated spontaneous mutation rates at the 6-thioguanine- and diphtheria-toxin-resistant loci. In contrast, the TdR-auxotrophic 'revertant' did not show this property. Similar results were obtained by the multiple replating technique. From these comparative studies and other previous characterizations, it appears that a single gene mutation is responsible for the following pleiotropic phenotype: slow growth. UV sensitivity, high UV-induced mutability, high frequency of site-specific bromodeoxyuridine (BrdU)-dependent chromosome breaks and enhanced spontaneous mutation rate. Recent studies indicate that the mutation may be on the gene for DNA polymerase alpha. The results further indicate that thymidine auxotrophy or imbalance in nucleotide pools is not necessarily associated with the mutator activity in mammalian cells.