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

摘要

The tumor suppressor BRCA2 is essential for homologousrecombination (HR), replication fork stability,and DNA interstrand crosslink repair in vertebrates.We identify HSF2BP, a protein previously describedas testis specific and not characterized functionally,as an interactor of BRCA2 in mouse embryonicstem cells, where the 2 proteins form a constitutivecomplex. HSF2BP is transcribed in all cultured humancancer cell lines tested and elevated in some tumorsamples. Inactivation of the mouse Hsf2bp generesults in male infertility due to a severe HR defectduring spermatogenesis. The BRCA2-HSF2BP interactionis highly evolutionarily conserved and maps toarmadillo repeats in HSF2BP and a 68-amino acidregion between the BRC repeats and the DNA bindingdomain of human BRCA2 (Gly2270-Thr2337)encoded by exons 12 and 13. This region of BRCA2does not harbor known cancer-associated missensemutations and may be involved in the reproductiverather than the tumor-suppressing function ofBRCA2.