Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry

作者：Zhao Weixing; Vaithiyalingam Sivaraja; Filippo Joseph San; Maranon David G; Jimenez Sainz Judit; Fontenay Gerald V; Kwon Youngho; Leung Stanley G; Lu Lucy; Jensen Ryan B; Chazin Walter J; Wiese Claudia; Sung Patrick

来源：Molecular Cell, 2015, 59(2): 176-187.

DOI：10.1016/j.molcel.2015.05.032

The tumor suppressor BRCA2 is thought to facilitate the handoff of ssDNA from replication protein A (RPA) to the RAD51 recombinase during DNA break and replication fork repair by homologous recombination. However, we find that RPA-RAD51 exchange requires the BRCA2 partner DSS1. Biochemical, structural, and in vivo analyses reveal that DSS1 allows the BRCA2-DSS1 complex to physically and functionally interact with RPA. Mechanistically, DSS1 acts as a DNA mimic to attenuate the affinity of RPA for ssDNA. A mutation in the solvent-exposed acidic domain of DSS1 compromises the efficacy of RPA-RAD51 exchange. Thus, by targeting RPA and mimicking DNA, DSS1 functions with BRCA2 in a two-component homologous recombination mediator complex in genome maintenance and tumor suppression. Our findings may provide a paradigm for understanding the roles of DSS1 in other biological processes.

• 出版日期2015-7-16