The Landscape of Mouse Meiotic Double-Strand Break Formation, Processing, and Repair

Cell. 2016 Oct 20;167(3):695-708.e16. doi: 10.1016/j.cell.2016.09.035. Epub 2016 Oct 13.


Heritability and genome stability are shaped by meiotic recombination, which is initiated via hundreds of DNA double-strand breaks (DSBs). The distribution of DSBs throughout the genome is not random, but mechanisms molding this landscape remain poorly understood. Here, we exploit genome-wide maps of mouse DSBs at unprecedented nucleotide resolution to uncover previously invisible spatial features of recombination. At fine scale, we reveal a stereotyped hotspot structure-DSBs occur within narrow zones between methylated nucleosomes-and identify relationships between SPO11, chromatin, and the histone methyltransferase PRDM9. At large scale, DSB formation is suppressed on non-homologous portions of the sex chromosomes via the DSB-responsive kinase ATM, which also shapes the autosomal DSB landscape at multiple size scales. We also provide a genome-wide analysis of exonucleolytic DSB resection lengths and elucidate spatial relationships between DSBs and recombination products. Our results paint a comprehensive picture of features governing successive steps in mammalian meiotic recombination.

Keywords: DNA damage; DNA repair; PRDM9; SPO11; chromatin; double-strand break; homologous recombination; meiosis; mouse; resection.

Publication types

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

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA Breaks, Double-Stranded*
  • DNA Methylation
  • DNA Repair*
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism
  • Genomic Instability / genetics*
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism
  • Homologous Recombination*
  • Meiosis / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Nucleosomes / enzymology
  • Nucleosomes / genetics
  • X Chromosome / genetics
  • Y Chromosome / genetics


  • Chromatin
  • Nucleosomes
  • Histone-Lysine N-Methyltransferase
  • prdm9 protein, mouse
  • Ataxia Telangiectasia Mutated Proteins
  • Atm protein, mouse
  • Endodeoxyribonucleases
  • meiotic recombination protein SPO11