BRCA2 binding through a cryptic repeated motif to HSF2BP oligomers does not impact meiotic recombination.
Animals
BRCA2 Protein
/ genetics
Cell Cycle Proteins
/ genetics
Cells, Cultured
Crystallography, X-Ray
/ methods
Female
Homologous Recombination
Humans
Magnetic Resonance Spectroscopy
Male
Meiosis
Mice
Models, Animal
Protein Interaction Domains and Motifs
Sequence Deletion
Spermatogenesis
/ physiology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 07 2021
29 07 2021
Historique:
received:
22
01
2021
accepted:
12
07
2021
entrez:
30
7
2021
pubmed:
31
7
2021
medline:
25
8
2021
Statut:
epublish
Résumé
BRCA2 and its interactors are required for meiotic homologous recombination (HR) and fertility. Loss of HSF2BP, a BRCA2 interactor, disrupts HR during spermatogenesis. We test the model postulating that HSF2BP localizes BRCA2 to meiotic HR sites, by solving the crystal structure of the BRCA2 fragment in complex with dimeric armadillo domain (ARM) of HSF2BP and disrupting this interaction in a mouse model. This reveals a repeated 23 amino acid motif in BRCA2, each binding the same conserved surface of one ARM domain. In the complex, two BRCA2 fragments hold together two ARM dimers, through a large interface responsible for the nanomolar affinity - the strongest interaction involving BRCA2 measured so far. Deleting exon 12, encoding the first repeat, from mBrca2 disrupts BRCA2 binding to HSF2BP, but does not phenocopy HSF2BP loss. Thus, results herein suggest that the high-affinity oligomerization-inducing BRCA2-HSF2BP interaction is not required for RAD51 and DMC1 recombinase localization in meiotic HR.
Identifiants
pubmed: 34326328
doi: 10.1038/s41467-021-24871-6
pii: 10.1038/s41467-021-24871-6
pmc: PMC8322138
doi:
Substances chimiques
BRCA2 Protein
0
BRCA2 protein, human
0
Cell Cycle Proteins
0
HSF2BP protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4605Informations de copyright
© 2021. The Author(s).
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