Molecular structures and mechanisms of DNA break processing in mouse meiosis

Shintaro Yamada, Anjali Gupta Hinch, Hisashi Kamido, Yongwei Zhang, Winfried Edelmann, Scott Keeney

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Exonucleolytic resection, critical to repair double-strand breaks (DSBs) by recombination, is not well understood, particularly in mammalian meiosis. Here, we define structures of resected DSBs in mouse spermatocytes genome-wide at nucleotide resolution. Resection tracts averaged 1100 nt, but with substantial fine-scale heterogeneity at individual hot spots. Surprisingly, EXO1 is not the major 5 → 3 exonuclease, but the DSB-responsive kinase ATM proved a key regulator of both initiation and extension of resection. In wild type, apparent intermolecular recombination intermediates clustered near to but offset from DSB positions, consistent with joint molecules with incompletely invaded 3 ends. Finally, we provide evidence for PRDM9-dependent chromatin remodeling leading to increased accessibility at recombination sites. Our findings give insight into the mechanisms of DSB processing and repair in meiotic chromatin.

Original languageEnglish (US)
Pages (from-to)806-818
Number of pages13
JournalGenes and Development
Volume34
Issue number11-12
DOIs
StatePublished - Jun 1 2020

Keywords

  • ATM
  • Chromatin
  • DNA double-strand breaks
  • EXO1
  • Meiosis
  • PRDM9
  • Recombination
  • Resection

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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