Multiple barriers to nonhomologous DNA end joining during meiosis in Drosophila

Genetics. 2012 Jul;191(3):739-46. doi: 10.1534/genetics.112.140996. Epub 2012 Apr 27.

Abstract

Repair of meiotic double-strand breaks (DSBs) uses the homolog and recombination to yield crossovers while alternative pathways such as nonhomologous end joining (NHEJ) are suppressed. Our results indicate that NHEJ is blocked at two steps of DSB repair during meiotic prophase: first by the activity of the MCM-like protein MEI-218, which is required for crossover formation, and, second, by Rad51-related proteins SPN-B (XRCC3) and SPN-D (RAD51C), which physically interact and promote homologous recombination (HR). We further show that the MCM-like proteins also promote the activity of the DSB repair checkpoint pathway, indicating an early requirement for these proteins in DSB processing. We propose that when a meiotic DSB is formed in the absence of both MEI-218 and SPN-B or SPN-D, a DSB substrate is generated that can enter the NHEJ repair pathway. Indeed, due to its high error rate, multiple barriers may have evolved to prevent NHEJ activity during meiosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism
  • DNA Breaks, Double-Stranded
  • DNA End-Joining Repair*
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Egg Proteins / genetics
  • Egg Proteins / metabolism
  • Female
  • Meiosis / genetics*
  • Mutation

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Egg Proteins
  • X-ray repair cross complementing protein 3
  • mei-218 protein, Drosophila
  • spn-B protein, Drosophila