RNase H1 facilitates recombinase recruitment by degrading DNA-RNA hybrids during meiosis

Nucleic Acids Res. 2023 Aug 11;51(14):7357-7375. doi: 10.1093/nar/gkad524.

Abstract

DNA-RNA hybrids play various roles in many physiological progresses, but how this chromatin structure is dynamically regulated during spermatogenesis remains largely unknown. Here, we show that germ cell-specific knockout of Rnaseh1, a specialized enzyme that degrades the RNA within DNA-RNA hybrids, impairs spermatogenesis and causes male infertility. Notably, Rnaseh1 knockout results in incomplete DNA repair and meiotic prophase I arrest. These defects arise from the altered RAD51 and DMC1 recruitment in zygotene spermatocytes. Furthermore, single-molecule experiments show that RNase H1 promotes recombinase recruitment to DNA by degrading RNA within DNA-RNA hybrids and allows nucleoprotein filaments formation. Overall, we uncover a function of RNase H1 in meiotic recombination, during which it processes DNA-RNA hybrids and facilitates recombinase recruitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA / genetics
  • DNA / metabolism
  • Humans
  • Male
  • Meiosis*
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Recombinases / genetics
  • Ribonuclease H* / metabolism
  • Spermatocytes / metabolism

Substances

  • Cell Cycle Proteins
  • DNA
  • Rad51 Recombinase
  • Recombinases
  • ribonuclease HI
  • Ribonuclease H