Shu complex SWS1-SWSAP1 promotes early steps in mouse meiotic recombination

Nat Commun. 2018 Oct 10;9(1):3961. doi: 10.1038/s41467-018-06384-x.

Abstract

The DNA-damage repair pathway homologous recombination (HR) requires factors that promote the activity of strand-exchange protein RAD51 and its meiosis-specific homolog DMC1. Here we show that the Shu complex SWS1-SWSAP1, a candidate for one such HR regulator, is dispensable for mouse viability but essential for male and female fertility, promoting the assembly of RAD51 and DMC1 on early meiotic HR intermediates. Only a fraction of mutant meiocytes progress to form crossovers, which are crucial for chromosome segregation, demonstrating crossover homeostasis. Remarkably, loss of the DNA damage checkpoint kinase CHK2 rescues fertility in females without rescuing crossover numbers. Concomitant loss of the BRCA2 C terminus aggravates the meiotic defects in Swsap1 mutant spermatocytes, suggesting an overlapping role with the Shu complex during meiotic HR. These results demonstrate an essential role for SWS1-SWSAP1 in meiotic progression and emphasize the complex interplay of factors that ensure recombinase function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BRCA2 Protein / chemistry
  • BRCA2 Protein / metabolism
  • Base Sequence
  • Cell Cycle Proteins / metabolism
  • Checkpoint Kinase 2 / genetics
  • Chromosome Pairing
  • Crossing Over, Genetic
  • DNA / metabolism
  • Female
  • Infertility / pathology
  • Male
  • Meiosis*
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutation / genetics
  • Nuclear Proteins / metabolism
  • Phosphate-Binding Proteins
  • Rad51 Recombinase / metabolism
  • Recombination, Genetic* / genetics
  • Spermatozoa / metabolism

Substances

  • BRCA2 Protein
  • Cell Cycle Proteins
  • Dmc1 protein, mouse
  • Nuclear Proteins
  • Phosphate-Binding Proteins
  • DNA
  • Checkpoint Kinase 2
  • Chek2 protein, mouse
  • Rad51 Recombinase