RNA-DNA hybrids regulate meiotic recombination

Cell Rep. 2021 Dec 7;37(10):110097. doi: 10.1016/j.celrep.2021.110097.

Abstract

RNA-DNA hybrids are often associated with genome instability and also function as a cellular regulator in many biological processes. In this study, we show that accumulated RNA-DNA hybrids cause multiple defects in budding yeast meiosis, including decreased sporulation efficiency and spore viability. Further analysis shows that these RNA-DNA hybrid foci colocalize with RPA/Rad51 foci on chromosomes. The efficient formation of RNA-DNA hybrid foci depends on Rad52 and ssDNA ends of meiotic DNA double-strand breaks (DSBs), and their number is correlated with DSB frequency. Interestingly, RNA-DNA hybrid foci and recombination foci show similar dynamics. The excessive accumulation of RNA-DNA hybrids around DSBs competes with Rad51/Dmc1, impairs homolog bias, and decreases crossover and noncrossover recombination. Furthermore, precocious removal of RNA-DNA hybrids by RNase H1 overexpression also impairs meiotic recombination similarly. Taken together, our results demonstrate that RNA-DNA hybrids form at ssDNA ends of DSBs to actively regulate meiotic recombination.

Keywords: DNA double-strand break; RNA-DNA hybrid; RNase H; crossover; meiosis; meiotic recombination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA Breaks, Double-Stranded
  • DNA Breaks, Single-Stranded
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Homologous Recombination*
  • Meiosis*
  • Nucleic Acid Conformation
  • Nucleic Acid Heteroduplexes / genetics
  • Nucleic Acid Heteroduplexes / metabolism*
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism*
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Replication Protein A / genetics
  • Replication Protein A / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • DMC1 protein, S cerevisiae
  • DNA, Fungal
  • DNA-Binding Proteins
  • Nucleic Acid Heteroduplexes
  • RFA1 protein, S cerevisiae
  • RNA, Fungal
  • Replication Protein A
  • Saccharomyces cerevisiae Proteins
  • RAD51 protein, S cerevisiae
  • Rad51 Recombinase