Diploid-associated adaptation to chronic low-dose UV irradiation requires homologous recombination in Saccharomyces cerevisiae.

UV-induced DNA lesions impede DNA replication and transcription, and are therefore a potential source of genome instability. Here, we performed serial transfer experiments on nucleotide excision repair (NER)-deficient (rad14Δ) yeast cells in the presence of chronic low-dose UV (CLUV) irradiation, focusing on the mechanisms underlying adaptive responses to CLUV irradiation. Our results show that the entire haploid rad14Δ population rapidly becomes diploid during CLUV exposure, and the evolved diploid rad14Δ cells were more CLUV-resistant than haploid cells. Strikingly, single-stranded DNA (ssDNA), but not pyrimidine dimer, accumulation is associated with diploid-dependent fitness in response to CLUV stress, suggesting that efficient repair of ssDNA tracts is beneficial for CLUV tolerance. Consistent with this hypothesis, homologous recombination (HR) is essential for the rapid evolutionary adaptation of diploidy, and rad14Δ cells lacking Rad51 recombinase, a key player in HR, exhibited abnormal cell morphology characterized by multiple RPA-YFP foci after CLUV exposure. Furthermore, interhomolog recombination is increased in CLUV-exposed rad14Δ diploids, which causes frequent loss of heterozygosity. Thus, our results highlight the importance of HR in the survival and genomic stability of cells with unrepaired lesions.