Dissecting the RAD51-BRC4 Interaction Landscape through Integrative Molecular Simulations and Experimental Biophysics.

ABSTRACT: The interaction between the RAD51 and BRCA2 proteins is central to homologous recombination (HR), a crucial pathway ensuring high-fidelity DNA repair. Recruitment of RAD51 involves eight highly conserved regions on BRCA2, named BRC repeats. The interaction between the fourth BRC repeat (BRC4) and the RAD51 C-terminal domain has been structurally characterized, while the complex of full-length RAD51 with the peptide remains elusive. This gap limits our understanding of cytosolic RAD51 recruitment driven by the BRCA2 BRC repeats, which is one of the first crucial steps in HR. Here, we report an integrative experimental and in silico approach to reconstruct the conformational ensemble in solution for full-length RAD51 in complex with BRC4. We combined AlphaFold2, cross-linking mass spe

SUBMITTER: Bresciani V 

PROVIDER: S-EPMC12606624 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature