Abstract
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 invivo analyses reveal that DSS1 allows the BRCA2-DSS1 complex to physically andfunctionally 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.
Original language | English (US) |
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Pages (from-to) | 176-187 |
Number of pages | 12 |
Journal | Molecular Cell |
Volume | 59 |
Issue number | 2 |
DOIs | |
State | Published - Jul 16 2015 |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology