Homologous Recombination and Repair Functions Required for Mutagenicity during Yeast Meiosis

Several meiotic events reshape the genome prior to its transfer (via gametes) to the next generation. The occurrence of new meiotic mutations is tightly linked to homologous recombination (HR) and firmly depends on Spo11-induced DNA breaks. To gain insight into the molecular mechanisms governing mutagenicity during meiosis, we examined the timing of mutation and recombination events in cells deficient in various DNA HR-repair genes, which represent distinct functions along the meiotic recombination process. Despite sequence similarities and overlapping activities of the two DNA translocases, Rad54 and Tid1, we observed essential differences in their roles in meiotic mutation occurrence: in the absence of Rad54, meiotic mutagenicity was elevated 8-fold compared to the wild type (WT), while in the tid1 Delta mutant, there were few meiotic mutations, nine percent compared to the WT. We propose that the presence of Rad54 channels recombinational repair to a less mutagenic pathway, whereas repair assisted by Tid1 is more mutagenic. A 3.5-fold increase in mutation level was observed in dmc1 increment cells, suggesting that single-stranded DNA (ssDNA) may be a potential source for mutagenicity during meiosis. Taken together, we suggest that the introduction of de novo mutations also contributes to the diversification role of meiotic recombination. These rare meiotic mutations revise genomic sequences and may contribute to long-term evolutionary changes.

Automated summary

Several events occur during meiosis to reshape the genome and transfer it to the next generation. The occurrence of new meiotic mutations is closely linked to homologous recombination and depends on Spo11-induced DNA breaks. Through studying the timing of mutation and recombination events in cells deficient in DNA HR-repair genes, we found that Rad54 and Tid1 play different roles in meiotic mutation occurrence. We also observed that single-stranded DNA may be a potential source for mutagenicity during meiosis. Overall, we propose that de novo mutations during meiosis contribute to the diversification of the genome.