The landscape of mouse meiotic double-strand break formation, processing, and repair

• Julian Lange ^[1] ; Shintaro Yamada ^[1] ; Sam E. Tischfield ^[1]
  1. [1] Memorial Sloan Kettering Cancer Center

     Memorial Sloan Kettering Cancer Center

     Estados Unidos

     
• Localización: Cell, ISSN 0092-8674, Vol. 167, Nº. 3, 2016, págs. 695-708
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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.