HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis
HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis
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DOI：
10.1016/j.celrep.2019.05.096
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发表时间：
2019-06-25
期刊：
影响因子：
8.8
通讯作者：
Zelensky, Alex N.
中科院分区：
文献类型：
--
作者：
Brandsma, Inger;Sato, Koichi;Zelensky, Alex N.
肿瘤抑制因子BRCA 2对于脊椎动物中的同源重组（HR）、复制叉稳定性和DNA链间交联修复是必不可少的。我们确定HSF 2BP，一种以前被描述为睾丸特异性的蛋白质，功能上没有特征，作为小鼠胚胎干细胞中BRCA 2的相互作用物，其中2种蛋白质形成组成性复合物。HSF 2BP在测试的所有培养的人癌细胞系中转录，并且在一些肿瘤样品中升高。小鼠Hsf 2bp基因的失活由于精子发生期间严重的HR缺陷而导致雄性不育。BRCA 2-HSF 2BP相互作用在进化上高度保守，并映射到HSF 2BP中的犰狳重复序列和BRC重复序列与由外显子12和13编码的人BRCA 2的DNA结合结构域（Gly 2270-Thr 2337）之间的68个氨基酸区域。BRCA 2的这一区域没有已知的癌症相关错义突变，可能与BRCA 2的生殖功能有关，而不是肿瘤抑制功能。
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.