Abstract
Mutations in diploid budding yeast occur in meiosis at higher frequencies than in cells grown vegetatively. Such meiotic mutations are thought to result from the repair of double-strand breaks (DSBs) in meiosis, during the process of recombination. Here, we report studies of mutagenicity in haploid strains that may undergo meiosis due to the expression of both mating-type alleles, MATa and MATα. We measure the rate of mutagenicity in the reporter gene CAN1, and find it to be fivefold higher than in mitotic cells, as determined by fluctuation analysis. This enhanced meiotic mutagenicity is shown to depend on the presence of SPO11, the gene responsible for meiotic DSBs. Mutations in haploid meiosis must result from repair of the DSBs through interaction with the sister chromatid, rather than with non-sister chromatids as in diploids. Thus, mutations in diploid meiosis that are not ostensibly associated with recombination events can be explained by sister-chromatid repair. The spectrum of meiotic mutations revealed by Sanger sequencing is similar in haploid and in diploid meiosis. Compared to mitotic mutations in CAN1, long Indels are more frequent among meiotic mutations. Both, meiotic and mitotic mutations are more common at G/C sites than at A/T, in spite of an opposite bias in the target reporter gene. We conclude that sister-chromatid repair of DSBs is a major source of mutagenicity in meiosis.
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Acknowledgements
We thank our colleague Dr. Tanvi Suhane for her useful comments on the manuscript.
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Supported by funds provided by the Israel Science Foundation (Grants No. 501/16 and 397/20), the US-Israel Binational Science Foundation (Grant No. 2009299) and by Hadassah Academic College.
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Conceived and designed the experiments: GS, AAE. Performed the experiments: OM, LM. Contributed reagents/materials/analysis tools: DZ, LM. Wrote the paper: GS.
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Simchen, G., Mansour, O., Morciano, L. et al. Mutagenicity in haploid yeast meiosis resulting from repair of DSBs by the sister chromatid. Curr Genet 67, 799–806 (2021). https://doi.org/10.1007/s00294-021-01189-w
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DOI: https://doi.org/10.1007/s00294-021-01189-w