A pathway for error-free non-homologous end joining of resected meiotic double-strand breaks

Nucleic Acids Res. 2021 Jan 25;49(2):879-890. doi: 10.1093/nar/gkaa1205.


Programmed DNA double-strand breaks (DSBs) made during meiosis are repaired by recombination with the homologous chromosome to generate, at selected sites, reciprocal crossovers that are critical for the proper separation of homologs in the first meiotic division. Backup repair processes can compensate when the normal meiotic recombination processes are non-functional. We describe a novel backup repair mechanism that occurs when the homologous chromosome is not available in Drosophila melanogaster meiosis. In the presence of a previously described mutation (Mcm5A7) that disrupts chromosome pairing, DSB repair is initiated by homologous recombination but is completed by non-homologous end joining (NHEJ). Remarkably, this process yields precise repair products. Our results provide support for a recombination intermediate recently proposed in mouse meiosis, in which an oligonucleotide bound to the Spo11 protein that catalyzes DSB formation remains bound after resection. We propose that this oligonucleotide functions as a primer for fill-in synthesis to allow scarless repair by NHEJ. We argue that this is a conserved repair mechanism that is likely to be invoked to overcome occasional challenges in normal meiosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Computer Simulation
  • Crossing Over, Genetic
  • DNA Breaks, Double-Stranded*
  • DNA End-Joining Repair / genetics*
  • DNA Ligase ATP / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / genetics*
  • Endodeoxyribonucleases / physiology
  • Female
  • Male
  • Meiosis / genetics*
  • Models, Genetic
  • Mutation, Missense
  • Oligonucleotides / genetics*
  • Point Mutation
  • Polymorphism, Single Nucleotide
  • Rad51 Recombinase / physiology
  • Sequence Alignment
  • Sequence Deletion
  • Whole Genome Sequencing


  • Cell Cycle Proteins
  • Drosophila Proteins
  • Mcm5 protein, Drosophila
  • Oligonucleotides
  • Rad51 Recombinase
  • spn-A protein, Drosophila
  • Endodeoxyribonucleases
  • meiotic recombination protein SPO11
  • DNA Ligase ATP