First Author | Lange J | Year | 2016 |
Journal | Cell | Volume | 167 |
Issue | 3 | Pages | 695-708.e16 |
PubMed ID | 27745971 | Mgi Jnum | J:238088 |
Mgi Id | MGI:5818093 | Doi | 10.1016/j.cell.2016.09.035 |
Citation | Lange J, et al. (2016) The Landscape of Mouse Meiotic Double-Strand Break Formation, Processing, and Repair. Cell 167(3):695-708.e16 |
abstractText | 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. |