Different mating type-regulated genes affect the DNA repair defects in Saccharomyces RAD51, RAD52 and RAD55 mutants

Saccharomyces cerevisiae cells expressing both a and mating-type (MAT) genes (termed mating-type heterozygosity) exhibit higher rates of spontaneous recombination and greater radiation-resistance than cells expressing only MATa or MAT. MAT heterozygosity suppresses recombination defects of four mutations involved in homologous recombination: complete deletions of RAD55 or RAD57, an ATPase-defective Rad51 mutation (rad51-K191R), and a C-terminal truncation of Rad52, rad52-327. We investigated the genetic basis of MAT-dependent suppression of these mutants by deleting genes whose expression is controlled by the Mata1-Mat2 repressor and scoring resistance to both campothecin (CPT) and phleomycin. Haploid rad55 strains became more damage-resistant after deleting genes required for nonhomologous end-joining (NHEJ), a process that is repressed in MATa/MAT cells. Surprisingly, NHEJ mutations do not suppress CPT sensitivity of rad51-K191R or rad52-327. However, rad51-K191R is uniquely suppressed by deleting the RME1 gene encoding a repressor of meiosis or its co-regulator SIN4; this effect is independent of the meiosis-specific homolog, Dmc1. Sensitivity of rad52-327 to CPT was unexpectedly increased by the MATa/MAT-repressed gene YGL193C, emphasizing the complex ways in which MAT regulates homologous recombination. The rad52-327 mutation is suppressed by deleting the prolyl isomerase Fpr3, which is not MAT-regulated. rad55 is also suppressed by deletion of PST2 and/or YBR052C (RFS1, rad55 suppressor), two members of a 3-gene family of flavodoxin-fold proteins that associate in a nonrandom fashion with chromatin. All three recombination-defective mutations are made more sensitive by deletions of Rad6 and of the histone deacetylases Rpd3 and Ume6, although these mutations are not themselves CPT- or phleomycin-sensitive.

Key Words: RAD mutants, mating-type, suppression, yeast

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