Abstract: In order to help further define DNA post-replication repair (PRR), a conditional synthetic lethal screen was employed to identify new genes involved in the PRR pathway. A synthetic lethal screen with the mms2 mutation resulted in the recovery of two suppressor mutations responsible for regulating PRR. The recovered suppressors are the mating type genes and SIR3. Indeed, controlled expression of both mating type genes or deletion of SIR3 rescued the conditional synthetic lethal mutant phenotypes. Furthermore, comprehensive analyses suggest that mating type heterozygosity confers tolerance to a broad range of DNA damage, and that this effect is limited to all PRR pathway mutations, but does not apply to base excision repair, nucleotide excision repair or recombination repair mutants. In addition, the tolerance conferred to PRR mutants as a result of mating type heterozygosity is dependent on a functional homologous recombination but not the non-homologous end-joining pathway. Thus, mating type status appears to be responsible for signalling DNA content and possibly cell cycle stage, allowing the cell to select the most efficient means to repair the DNA damage.