A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination.
Animals
BRCA2 Protein
/ metabolism
Cell Cycle Proteins
/ genetics
Cell Line
Chromosomal Proteins, Non-Histone
/ metabolism
DNA Breaks, Double-Stranded
DNA Repair
DNA-Binding Proteins
/ genetics
Female
Gene Knockout Techniques
Homologous Recombination
Male
Meiosis
/ physiology
Mice
Nuclear Proteins
/ metabolism
Phosphate-Binding Proteins
Rad51 Recombinase
/ metabolism
Recombinases
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 02 2019
13 02 2019
Historique:
received:
02
08
2018
accepted:
22
01
2019
entrez:
15
2
2019
pubmed:
15
2
2019
medline:
12
4
2019
Statut:
epublish
Résumé
Homologous recombination (HR) repairs DNA double-strand breaks (DSBs) to maintain genomic integrity. Recombinase recruited to the DSBs by the mediator protein BRCA2 catalyzes the homology-directed repair. During meiotic HR, programmed DSBs are introduced genome-wide but their repair mechanisms, including the regulation of BRCA2, have remained largely elusive. Here we identify a meiotic localizer of BRCA2, MEILB2/HSF2BP, that localizes to the site of meiotic DSBs in mice. Disruption of Meilb2 abolishes the localization of RAD51 and DMC1 recombinases in spermatocytes, leading to errors in DSB repair and male sterility. MEILB2 directly binds to BRCA2 and regulates its association to meiotic DSBs. We map the MEILB2-binding domain within BRCA2 that is distinct from the canonical DNA-binding domain but is sufficient to localize to meiotic DSBs in a MEILB2-dependent manner. We conclude that localization of BRCA2 to meiotic DSBs is mediated by MEILB2, which is an integral mechanism to repair abundant meiotic DSBs.
Identifiants
pubmed: 30760716
doi: 10.1038/s41467-019-08676-2
pii: 10.1038/s41467-019-08676-2
pmc: PMC6374363
doi:
Substances chimiques
BRCA2 Protein
0
BRCA2 protein, mouse
0
Cell Cycle Proteins
0
Chromosomal Proteins, Non-Histone
0
DNA-Binding Proteins
0
Dmc1 protein, mouse
0
Nuclear Proteins
0
Phosphate-Binding Proteins
0
Recombinases
0
Rad51 Recombinase
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
722Commentaires et corrections
Type : ErratumIn
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