HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis | Zendy

Inger Brandsma | Zendy; Koichi Sato | Zendy; Sari E. van Rossum-Fikkert | Zendy; Nicole van Vliet | Zendy; Esther Sleddens | Zendy; Marcel Reuter | Zendy; Hanny Odijk | Zendy; Nathalie van den Tempel | Zendy; Dick H. W. Dekkers | Zendy; Karel Bezstarosti | Zendy; Jeroen Demmers | Zendy; Alex Maas | Zendy; Joyce H.G. Lebbink | Zendy; Claire Wyman | Zendy; Jeroen Essers | Zendy; Dik C. van Gent | Zendy; Willy M. Baarends | Zendy; Puck Knipscheer | Zendy; Roland Kanaar | Zendy; Alex N. Zelensky | Zendy

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HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis

Author(s) -

Inger Brandsma,

Koichi Sato,

Sari E. van Rossum-Fikkert,

Nicole van Vliet,

Esther Sleddens,

Marcel Reuter,

Hanny Odijk,

Nathalie van den Tempel,

Dick H. W. Dekkers,

Karel Bezstarosti,

Jeroen Demmers,

Alex Maas,

Joyce H.G. Lebbink,

Claire Wyman,

Jeroen Essers,

Dik C. van Gent,

Willy M. Baarends,

Puck Knipscheer,

Roland Kanaar,

Alex N. Zelensky

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.05.096

Subject(s) - biology , homologous recombination , gene , genetics , rad51 , exon , brca2 protein , armadillo , germline , spermatogenesis , homologous chromosome , microbiology and biotechnology , germ cell , dna repair , missense mutation , mutation , germline mutation , endocrinology

The tumor suppressor BRCA2 is essential for homologous recombination (HR), replication fork stability, and DNA interstrand crosslink repair in vertebrates. We identify HSF2BP, a protein previously described as testis specific and not characterized functionally, as an interactor of BRCA2 in mouse embryonic stem cells, where the 2 proteins form a constitutive complex. HSF2BP is transcribed in all cultured human cancer cell lines tested and elevated in some tumor samples. Inactivation of the mouse Hsf2bp gene results in male infertility due to a severe HR defect during spermatogenesis. The BRCA2-HSF2BP interaction is highly evolutionarily conserved and maps to armadillo repeats in HSF2BP and a 68-amino acid region between the BRC repeats and the DNA binding domain of human BRCA2 (Gly2270-Thr2337) encoded by exons 12 and 13. This region of BRCA2 does not harbor known cancer-associated missense mutations and may be involved in the reproductive rather than the tumor-suppressing function of BRCA2.

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