ATM and PRDM9 regulate SPO11-bound recombination intermediates during meiosis

Jacob Paiano, Wei Wu, Shintaro Yamada, Nicholas Sciascia, Elsa Callen, Ana Paola Cotrim, Rajashree A. Deshpande, Yaakov Maman, Amanda Day, Tanya T. Paull and André Nussenzweig ()
Additional contact information
Jacob Paiano: Laboratory of Genome Integrity, National Cancer Institute, NIH
Wei Wu: Laboratory of Genome Integrity, National Cancer Institute, NIH
Shintaro Yamada: Molecular Biology Program, Memorial Sloan Kettering Cancer Center
Nicholas Sciascia: Laboratory of Genome Integrity, National Cancer Institute, NIH
Elsa Callen: Laboratory of Genome Integrity, National Cancer Institute, NIH
Ana Paola Cotrim: Laboratory of Genome Integrity, National Cancer Institute, NIH
Rajashree A. Deshpande: The Howard Hughes Medical Institute and The University of Texas at Austin
Yaakov Maman: Laboratory of Genome Integrity, National Cancer Institute, NIH
Amanda Day: Laboratory of Genome Integrity, National Cancer Institute, NIH
Tanya T. Paull: The Howard Hughes Medical Institute and The University of Texas at Austin
André Nussenzweig: Laboratory of Genome Integrity, National Cancer Institute, NIH

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Meiotic recombination is initiated by SPO11-induced double-strand breaks (DSBs). In most mammals, the methyltransferase PRDM9 guides SPO11 targeting, and the ATM kinase controls meiotic DSB numbers. Following MRE11 nuclease removal of SPO11, the DSB is resected and loaded with DMC1 filaments for homolog invasion. Here, we demonstrate the direct detection of meiotic DSBs and resection using END-seq on mouse spermatocytes with low sample input. We find that DMC1 limits both minimum and maximum resection lengths, whereas 53BP1, BRCA1 and EXO1 play surprisingly minimal roles. Through enzymatic modifications to END-seq, we identify a SPO11-bound meiotic recombination intermediate (SPO11-RI) present at all hotspots. We propose that SPO11-RI forms because chromatin-bound PRDM9 asymmetrically blocks MRE11 from releasing SPO11. In Atm–/– spermatocytes, trapped SPO11 cleavage complexes accumulate due to defective MRE11 initiation of resection. Thus, in addition to governing SPO11 breakage, ATM and PRDM9 are critical local regulators of mammalian SPO11 processing.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-14654-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14654-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-14654-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().