Mismatch repair and homologous recombination are yin-yang partners in hybrid zygote meiosis

Mismatch repair (MMR) is believed to prevent homologous recombination (HR) between homologous chromosomes, causing infertility in hybrids between closely related species. We report that HR and MMR are yin-yang partners in the response to genetic polymorphisms and that several budding yeast HR genes (i.e., RAD51 , RAD54 , ZMM ) exhibit anti-MMR activities. This yin-yang relationship biases MMR in wild-type interspecies ( Saccharomyces cerevisiae / Saccharomyces paradoxus ) hybrid zygotes and intraspecies S. cerevisiae hybrid zygotes with anti-MMR mutations, resulting in excessive (rather than insufficient) interhomolog HR, including negative crossover interference, allelic conversion or even disruption. The anti-MMR function of S. cerevisiae Rad54 prevails over its accessory role in promoting Rad51-mediated strand exchange during hybrid meiosis. Srs2 (the yeast ortholog of Esherichia coli UvrD helicase) facilitates the MMR system by dissembling Rad51-ssDNA presynaptic filaments. Sgs1 (the yeast ortholog of E. coli RecQ helicase) acts after MMR-dependent recognition of heteroduplex mismatches to promote crossover clustering and allelic switching.