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Cell Rep. 2019 Jun 25;27(13):3790-3798.e7. doi: 10.1016/j.celrep.2019.05.096.

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

Author information

1
Department of Molecular Genetics, Oncode Institute, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
2
Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
3
Department of Molecular Genetics, Oncode Institute, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands; Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
4
Department of Developmental Biology, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
5
Proteomics Center, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
6
Department of Cell Biology, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
7
Department of Molecular Genetics, Oncode 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.
8
Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands. Electronic address: p.knipscheer@hubrecht.eu.
9
Department of Molecular Genetics, Oncode Institute, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands. Electronic address: r.kanaar@erasmusmc.nl.
10
Department of Molecular Genetics, Oncode Institute, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands. Electronic address: a.zelensky@erasmusmc.nl.

Abstract

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.

KEYWORDS:

BRCA2; HSF2BP; homologous recombination; meiosis; spermatogenesis

PMID:
31242413
DOI:
10.1016/j.celrep.2019.05.096
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