BRCA2 binding through a cryptic repeated motif to HSF2BP oligomers does not impact meiotic recombination.

Autor: Ghouil R; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Uni Paris-Sud, Uni Paris-Saclay, Gif-sur-Yvette, France., Miron S; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Uni Paris-Sud, Uni Paris-Saclay, Gif-sur-Yvette, France., Koornneef L; Department of Developmental Biology, Oncode Institute, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands., Veerman J; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands., Paul MW; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands., Le Du MH; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Uni Paris-Sud, Uni Paris-Saclay, Gif-sur-Yvette, France., Sleddens-Linkels E; Department of Developmental Biology, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands., van Rossum-Fikkert SE; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands.; Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands., van Loon Y; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands., Felipe-Medina N; Molecular Mechanisms Program, Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), Salamanca, Spain., Pendas AM; Molecular Mechanisms Program, Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), Salamanca, Spain., Maas A; Department of Cell Biology, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands., Essers J; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands.; Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands.; Department of Vascular Surgery, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands., Legrand P; Synchrotron SOLEIL, L'Orme des Merisiers, Gif-sur-Yvette, France., Baarends WM; Department of Developmental Biology, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands., Kanaar R; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands. r.kanaar@erasmusmc.nl., Zinn-Justin S; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Uni Paris-Sud, Uni Paris-Saclay, Gif-sur-Yvette, France. Sophie.ZINN@cea.fr., Zelensky AN; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands. a.zelensky@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jul 29; Vol. 12 (1), pp. 4605. Date of Electronic Publication: 2021 Jul 29.
DOI: 10.1038/s41467-021-24871-6
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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