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

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.
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