GENETIC INTERACTIONS BETWEEN MUTANTS OF THE ERROR-PRONE REPAIR GROUP OF SACCHAROMYCES-CEREVISIAE AND THEIR EFFECT ON RECOMBINATION AND MUTAGENESIS

We have created an isogenic series of yeast strains that carry genetic systems to monitor different types of recombination and mutation [B. Liefshitz, A. Parket, R. Maya, M. Kupiec. The role of DNA repair genes in recombination between repeated sequences in yeast, Genetics 140 (1 995) 1199-1211.]. In the present study we characterize the effect of m utations in genes of the 'error-prone' or postreplicative repair group on recombination and mutation. We show that rad5 and rad18 strains ha ve elevated levels of spontaneous recombination, both of ectopic gene conversion and of recombination between direct repeats. The increase i n recombination levels is similar in both mutants and in the rad5 rad1 8 double mutant, suggesting that the RAD5 and RAD18 gene products act together with respect to spontaneous recombination. In contrast, RAD5 and RAD18 play alternative roles in mutagenic repair: mutations in eac h of these genes elevate spontaneous forward mutation at the CAN1 locu s, but when both genes are deleted, a low level of spontaneous mutagen esis is seen. The RAD5/RAD18 pathway of mutagenic repair is dependent on the REV3-encoded translesion polymerase. We analyze the interaction s between the RAD5 and RAD18 gene products and other repair genes. The high recombination levels seen in rad5 and rad18 mutants is dependent on the RAD1, RAD51, RAD52, and RAD57 genes. The Srs2 helicase plays a n important role in creating the recombinogenic substrate(s) processed by the RAD5 and RAD18 gene products. (C) 1998 Elsevier Science B.V.