| Literature DB >> 31242413 |
Inger Brandsma1, Koichi Sato2, Sari E van Rossum-Fikkert3, Nicole van Vliet1, Esther Sleddens4, Marcel Reuter1, Hanny Odijk1, Nathalie van den Tempel1, Dick H W Dekkers5, Karel Bezstarosti5, Jeroen A A Demmers5, Alex Maas6, Joyce Lebbink3, Claire Wyman3, Jeroen Essers7, Dik C van Gent1, Willy M Baarends4, Puck Knipscheer8, Roland Kanaar9, Alex N Zelensky10.
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.Entities:
Keywords: BRCA2; HSF2BP; homologous recombination; meiosis; spermatogenesis
Year: 2019 PMID： 31242413 DOI： 10.1016/j.celrep.2019.05.096
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423