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RNA-DNA hybrids regulate meiotic recombination.

Xuan Yang1, Binyuan Zhai2, Shunxin Wang2

  • 1Center for Reproductive Medicine, Cheeloo College of Medicine, State Key Laboratory of Microbial Technology, Shandong University, China.

Cell Reports
|December 8, 2021
PubMed
Summary

Accumulated RNA-DNA hybrids in budding yeast meiosis cause defects in sporulation and spore viability. These hybrids form at DNA double-strand breaks and regulate meiotic recombination by interacting with key proteins.

Keywords:
DNA double-strand breakRNA-DNA hybridRNase Hcrossovermeiosismeiotic recombination

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • RNA-DNA hybrids are implicated in genome instability and cellular regulation.
  • Their specific roles in meiosis, particularly during DNA double-strand break (DSB) repair, are not fully understood.

Purpose of the Study:

  • To investigate the role and impact of RNA-DNA hybrids during budding yeast meiosis.
  • To elucidate the mechanism by which RNA-DNA hybrids affect meiotic recombination and genome stability.

Main Methods:

  • Microscopy to visualize RNA-DNA hybrid foci and their colocalization with recombination proteins (RPA/Rad51).
  • Genetic analysis of budding yeast mutants (e.g., Rad52, RNase H1 overexpression) to assess the formation and impact of RNA-DNA hybrids.
  • Quantification of DSB frequency, sporulation efficiency, and spore viability.

Main Results:

  • Accumulated RNA-DNA hybrids lead to decreased sporulation efficiency and spore viability in yeast meiosis.
  • RNA-DNA hybrid foci colocalize with RPA/Rad51 foci and depend on Rad52 and meiotic DSBs.
  • Excessive RNA-DNA hybrids interfere with Rad51/Dmc1, impair homolog bias, and reduce both crossover and noncrossover recombination.
  • Early removal of RNA-DNA hybrids also impairs meiotic recombination.

Conclusions:

  • RNA-DNA hybrids form at the single-stranded DNA ends of meiotic DSBs.
  • These hybrids actively regulate meiotic recombination by influencing DSB repair pathways.
  • The dynamics and localization of RNA-DNA hybrids are critical for successful meiotic progression and genome integrity.