GENETIC-CONTROL OF ENHANCED MUTABILITY OF MITOCHONDRIAL-DNA AND GAMMA-RAY SENSITIVITY IN SACCHAROMYCES-CEREVISIAE

Five nuclear mutants enhancing the spontaneous mutation rate of mt[mitochondrial]DNA were isolated in S. cerevisiae. These mutators fall into 5 complementation groups and are located at 5 genetic loci different from rad50 to rad57 loci. Three mutants (gam1, gam2 and gam4), insensitive or weakly sensitive to .gamma.-rays, exhibit increased frequency of spontaneous production of mutants with large deletions of the mtDNA (.rho.-) and of all tested mitochondrial drug-resistant mutants. Two other mutants (gam3 and gam5), highly sensitive to .gamma.-rays, increase only the mutation rate of particular alleles of the mtDNA. The mutant gam5 enhances only the production of .rho.- and erythromycin-resistant clones. The mutant gam3 exhibits an enhanced rate of oligomycin-resistant clones as well as a collateral increase of nuclear mutability. The existence of gam3 and gam5 mutants indicates that at least 2 common steps contol both nuclear DNA repair and the mutability of particular alleles of the mtDNA. The general spontaneous mutability of the mtDNA includes at least 3 steps not involved in the repair of nuclear DNA, as revealed by the gam1, gam2 and gam4 mutations.