@article{025de30a025546128d1637a4d7e7f1ec,
title = "HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis",
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. BRCA2 is a key homologous recombination mediator in vertebrates. Brandsma et al. show that it directly interacts with a testis-expressed protein, HSF2BP, and that male mice deficient for HSF2BP are infertile due to a meiotic recombination defect. They also find that HSF2BP contributes to DNA repair in mouse embryonic stem cells.",
keywords = "BRCA2, homologous recombination, HSF2BP, meiosis, spermatogenesis",
author = "Inger Brandsma and Koichi Sato and {van Rossum-Fikkert}, {Sari E.} and {van Vliet}, Nicole and Esther Sleddens and Marcel Reuter and Hanny Odijk and {van den Tempel}, Nathalie and Dekkers, {Dick H.W.} and Karel Bezstarosti and Demmers, {Jeroen A.A.} and Alex Maas and Joyce Lebbink and Claire Wyman and Jeroen Essers and {van Gent}, {Dik C.} and Baarends, {Willy M.} and Puck Knipscheer and Roland Kanaar and Zelensky, {Alex N.}",
note = "Funding Information: The authors would like to thank Dr. John Martens for help with the analysis of the expression data and G. Stier from the European Molecular Biology Laboratory (EMBL) for providing pETM11 and pETM30. K.S. was supported by the Uehara Memorial Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, and the Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellowship for Research Abroad. P.K. was supported by the Netherlands Organisation for Scientific Research (VIDI 700.10.421) and a project grant from the Dutch Cancer Society (KWF HUBR 2015-7736). This research was funded by the Dutch Cancer Society and by the Gravitation Programme CancerGenomiCs.nl from the Netherlands Organisation for Scientific Research (NWO) and is part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. The research leading to these results has received funding from the European Community's Seventh Framework Program (FP7/2007-2013) under grant agreement HEALTH-F2-2010-259893, the Dutch Cancer Society (grant EMCR 2008-4045), and a Ride for the Roses cancer research grant. A.N.Z. and R.K. conceived the study. I.B. K.S. S.E.v.R.-F. M.R. H.O. N.v.d.T. and A.N.Z. performed the ESC and biochemical experiments. N.v.V. A.M. E.S. and A.N.Z. performed the mouse experiments. D.H.W.D. and K.B. collected the mass spectrometry data. J.A.A.D. J.L. C.W. J.E. D.C.v.G. W.M.B. P.K. A.N.Z. and R.K. supervised different parts of the study. A.N.Z. R.K. and P.K. wrote the manuscript, with contributions from the other authors. All of the authors read and approved the manuscript. The authors declare no competing interests. Funding Information: The authors would like to thank Dr. John Martens for help with the analysis of the expression data and G. Stier from the European Molecular Biology Laboratory (EMBL) for providing pETM11 and pETM30. K.S. was supported by the Uehara Memorial Foundation , the Mochida Memorial Foundation for Medical and Pharmaceutical Research , and the Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellowship for Research Abroad . P.K. was supported by the Netherlands Organisation for Scientific Research ( VIDI 700.10.421 ) and a project grant from the Dutch Cancer Society ( KWF HUBR 2015-7736 ). This research was funded by the Dutch Cancer Society and by the Gravitation Programme CancerGenomiCs.nl from the Netherlands Organisation for Scientific Research (NWO) and is part of the Oncode Institute, which is partly financed by the Dutch Cancer Society . The research leading to these results has received funding from the European Community{\textquoteright}s Seventh Framework Program ( FP7/2007-2013 ) under grant agreement HEALTH-F2-2010-259893 , the Dutch Cancer Society (grant EMCR 2008-4045 ), and a Ride for the Roses cancer research grant. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = jun,
day = "25",
doi = "10.1016/j.celrep.2019.05.096",
language = "English",
volume = "27",
pages = "3790--3798.e7",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}