Mouse MRE11-RAD50-NBS1 is needed to start and extend meiotic DNA end resection

Soonjoung Kim (), Shintaro Yamada, Tao Li, Claudia Canasto-Chibuque, Jun Hyun Kim, Marina Marcet-Ortega, Jiaqi Xu, Diana Y. Eng, Laura Feeney, John H. J. Petrini and Scott Keeney ()
Additional contact information
Soonjoung Kim: Memorial Sloan Kettering Cancer Center
Shintaro Yamada: Memorial Sloan Kettering Cancer Center
Tao Li: Memorial Sloan Kettering Cancer Center
Claudia Canasto-Chibuque: Memorial Sloan Kettering Cancer Center
Jun Hyun Kim: Memorial Sloan Kettering Cancer Center
Marina Marcet-Ortega: Memorial Sloan Kettering Cancer Center
Jiaqi Xu: Memorial Sloan Kettering Cancer Center
Diana Y. Eng: Memorial Sloan Kettering Cancer Center
Laura Feeney: Memorial Sloan Kettering Cancer Center
John H. J. Petrini: Memorial Sloan Kettering Cancer Center
Scott Keeney: Memorial Sloan Kettering Cancer Center

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Nucleolytic resection of DNA ends is critical for homologous recombination, but its mechanism is not fully understood, particularly in mammalian meiosis. Here we examine roles of the conserved MRN complex (MRE11, RAD50, and NBS1) through genome-wide analysis of meiotic resection during spermatogenesis in mice with various MRN mutations, including several that cause chromosomal instability in humans. Meiotic DSBs form at elevated levels but remain unresected if Mre11 is conditionally deleted, thus MRN is required for both resection initiation and regulation of DSB numbers. Resection lengths are reduced to varying degrees in MRN hypomorphs or if MRE11 nuclease activity is attenuated in a conditional nuclease-dead Mre11 model. These findings unexpectedly establish that MRN is needed for longer-range extension of resection beyond that carried out by the orthologous proteins in budding yeast meiosis. Finally, resection defects are additively worsened by combining MRN and Exo1 mutations, and mice that are unable to initiate resection or have greatly curtailed resection lengths experience catastrophic spermatogenic failure. Our results elucidate MRN roles in meiotic DSB end processing and establish the importance of resection for mammalian meiosis.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57928-x 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:16:y:2025:i:1:d:10.1038_s41467-025-57928-x

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

DOI: 10.1038/s41467-025-57928-x

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 ().