The tumor suppressor BRCA2 plays a key role in initiating homologous recombination by facilitating RAD51 filament formation on single-stranded DNA. The small acidic protein DSS1 is a crucial partner to BRCA2 in this process. In vitro and in cells (1,2), BRCA2 associates into oligomeric complexes besides also existing as monomers. A dimeric structure was further characterized by electron microscopic analysis (3), but the functional significance of the different BRCA2 assemblies remains to be determined. Here, we used biochemistry and electron microscopic imaging to demonstrate that the multimerization of BRCA2 is counteracted by DSS1 and ssDNA. When validating the findings, we identified three self-interacting regions and two types of self-association, the N-to-C terminal and the N-to-N terminal interactions. The N-to-C terminal self-interaction of BRCA2 is sensitive to DSS1 and ssDNA. The N-to-N terminal self-interaction is modulated by ssDNA. Our results define a novel role of DSS1 to regulate BRCA2 in an RPA-independent fashion. Since DSS1 is required for BRCA2 function in recombination, we speculate that the monomeric and oligomeric forms of BRCA2 might be active for different cellular events in recombinational DNA repair and replication fork stabilization.

中文翻译：

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DSS1 和 ssDNA 调节 BRCA2 的寡聚化。

肿瘤抑制因子 BRCA2 通过促进单链 DNA 上 RAD51 丝的形成，在启动同源重组中起着关键作用。在这个过程中，小酸性蛋白 DSS1 是 BRCA2 的重要伙伴。体外和细胞内（1、2)、BRCA2除以单体形式存在外，还可缔合成低聚复合物。通过电子显微镜分析进一步表征二聚体结构（3), 但不同 BRCA2 组件的功能意义仍有待确定。在这里，我们使用生物化学和电子显微镜成像来证明 BRCA2 的多聚化被 DSS1 和 ssDNA 抵消。在验证发现时，我们确定了三个自相互作用区域和两种类型的自关联，即 N-to-C 终端和 N-to-N 终端相互作用。BRCA2 的 N-to-C 末端自相互作用对 DSS1 和 ssDNA 敏感。N 到 N 末端自相互作用由 ssDNA 调制。我们的结果定义了 DSS1 以独立于 RPA 的方式调节 BRCA2 的新作用。由于重组中 BRCA2 功能需要 DSS1，