The Landscape of Mouse Meiotic Double-Strand Break Formation, Processing, and Repair.
Cell
; 167(3): 695-708.e16, 2016 Oct 20.
Article
em En
| MEDLINE
| ID: mdl-27745971
ABSTRACT
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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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Instabilidade Genômica
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Reparo do DNA
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Quebras de DNA de Cadeia Dupla
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Recombinação Homóloga
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Meiose
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos