Homologous recombination counteracts mismatch repair to promote fertility and genetic diversity
Dr. Wang, Ting-Fang - November, 2025
A research team led by Dr. Ting-Fang Wang published a research paper in the journal "Nucleic Acids Research" on September 3 this year. They found that several Baker’s yeast Saccharomyces cerevisiae proteins (Rad51, Rad54, and Rad59) that catalyze homologous recombination (HR) and ZMM proteins (Zip1, Zip4, Mer3, and Msh4) of the "synaptonemal complex (SC)" can all inhibit the activity of the mismatch repair (MMR) system during meiosis. MMR has long been considered a major obstacle to homeologous recombination (i.e., HR between similar but diverged DNA sequences) during sexual conjugation between Escherichia coli and Salmonella typhimurium, as well as hybrid meiosis between closely related eukaryotic species. Dr. Wang was then invited by Cell Press to publish a forum article in Trends in Genetics in October ? this year. It explains how they utilized whole-genome analysis data of meiotic products from intraspecies hybrid zygotes published in PNAS in 2021 to clarify a flaw in the widely accepted hypothesis that "MMR causes hybrid infertility and reproductive isolation between closely related species. Dr. Wang and collegues then applied “reverse genetic” to identify 12 HR mutant genes. These mutant genes specifically affect the fertility of interspecies hybrid zygotes but do not affect the fertility of purebred zygotes, demonstraing that multiple HR proteins can inhibit MMR activity and maintain genetic diversity. HR has long been considered the most faithful (highest fidelity) molecular mechanism for repairing damaged DNA, but their new findings have promoted a reconsideration of this hypothesis. Nearly 70 years after the discovery of the SC, this team also demonstrated for the first time that the true physiological function of SC in meiosis is to suppress MMR, thereby promoting genetic diversity in gamates or fungal sexual spores.
This work was supported by Academia Sinica and by National Science and Technology Council, Taiwan, ROC.
