@article{d9def238875b48759a2d46172fe8549f,
title = "Molecular structures and mechanisms of DNA break processing in mouse meiosis",
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.",
keywords = "ATM, Chromatin, DNA double-strand breaks, EXO1, Meiosis, PRDM9, Recombination, Resection",
author = "Shintaro Yamada and Hinch, {Anjali Gupta} and Hisashi Kamido and Yongwei Zhang and Winfried Edelmann and Scott Keeney",
note = "Funding Information: We thank A. Viale, N. Mohibullah, and R. Patel (Memorial Sloan Kettering Cancer Center [MSKCC] Integrated Genomics Operation) for sequencing and ATAC-seq library preparation; E. Mimitou for advice during adaptation of the S1-seq method; S. Peterson and M. Jasin (MSKCC), P. Donnelly (University of Oxford), A. Nussenzweig, W. Wu, and J. Paiano (National Institutes of Health) for discussions and sharing unpublished data; P.C. Huang (MSKCC) for ExoT treatment optimization; P.C. Huang and H. Murakami (MSKCC) for help in analysis of recombination intermediates; and M. Neale (University of Sussex) and members of the Keeney and Jasin laboratories for discussions. MSKCC core facilities were supported by National Institutes of Health (NIH) Cancer Center Core Grant P30 CA008748. This work was supported by NIH grant R35 GM118092 (to S.K.). Publisher Copyright: {\textcopyright} 2020 Cold Spring Harbor Laboratory Press. All rights reserved.",
year = "2020",
month = jun,
day = "1",
doi = "10.1101/gad.339309.120",
language = "English (US)",
volume = "34",
pages = "806--818",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "11-12",
}