BRCA2 and its interactors are required for meiotic homologous recombination (HR) and fertility. Loss of HSF2BP, a BRCA2 interactor, disrupts HR during spermatogenesis. We test the model postulating that HSF2BP localizes BRCA2 to meiotic HR sites, by solving the crystal structure of the BRCA2 fragment in complex with dimeric armadillo domain (ARM) of HSF2BP and disrupting this interaction in a mouse model. This reveals a repeated 23 amino acid motif in BRCA2, each binding the same conserved surface of one ARM domain. In the complex, two BRCA2 fragments hold together two ARM dimers, through a large interface responsible for the nanomolar affinity — the strongest interaction involving BRCA2 measured so far. Deleting exon 12, encoding the first repeat, from mBrca2 disrupts BRCA2 binding to HSF2BP, but does not phenocopy HSF2BP loss. Thus, results herein suggest that the high-affinity oligomerization-inducing BRCA2-HSF2BP interaction is not required for RAD51 and DMC1 recombinase localization in meiotic HR.

BRCA2 及其相互作用子是减数分裂同源重组 (HR) 和生育力所必需的。HSF2BP（一种 BRCA2 相互作用因子）的缺失会在精子发生过程中破坏 HR。我们通过解决与 HSF2BP 的二聚犰狳结构域 (ARM) 复合的 BRCA2 片段的晶体结构并在小鼠模型中破坏这种相互作用来测试假设 HSF2BP 将 BRCA2 定位到减数分裂 HR 位点的模型。这揭示了 BRCA2 中重复的 23 个氨基酸基序，每个基序都结合一个 ARM 结构域的相同保守表面。在复合物中，两个 BRCA2 片段通过负责纳摩尔亲和力的大界面将两个 ARM 二聚体结合在一起——迄今为止测量到的涉及 BRCA2 的最强相互作用。从mBrca2 中删除编码第一个重复的外显子 12破坏 BRCA2 与 HSF2BP 的结合，但不会表型复制 HSF2BP 丢失。因此，本文的结果表明，RAD51 和 DMC1 重组酶在减数分裂 HR 中的定位不需要高亲和力寡聚化诱导 BRCA2-HSF2BP 相互作用。