8GBJ

Cryo-EM structure of a human BCDX2/ssDNA complex

Summary for 8GBJ

• Entry DOI: 10.2210/pdb8gbj/pdb
• Related: 8FAZ
• EMDB information: 28961 29917
• Descriptor: DNA repair protein RAD51 homolog 2, DNA repair protein RAD51 homolog 3, DNA repair protein RAD51 homolog 4, ... (6 entities in total)
• Functional Keywords: dna binding protein, atp binding domain, homologous recombination, rad51 paralog, recombination, ssdna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 159596.29

Authors

Jia, L.,Wasmuth, E.V.,Ruben, E.A.,Sung, P.,Rawal, Y.,Greene, E.C.,Meir, A.,Olsen, S.K. (deposition date: 2023-02-26, release date: 2023-06-21, Last modification date: 2024-10-23)

Primary citation

Rawal, Y.,Jia, L.,Meir, A.,Zhou, S.,Kaur, H.,Ruben, E.A.,Kwon, Y.,Bernstein, K.A.,Jasin, M.,Taylor, A.B.,Burma, S.,Hromas, R.,Mazin, A.V.,Zhao, W.,Zhou, D.,Wasmuth, E.V.,Greene, E.C.,Sung, P.,Olsen, S.K.
Structural insights into BCDX2 complex function in homologous recombination.
Nature, 619:640-649, 2023

PubMed Abstract: Homologous recombination (HR) fulfils a pivotal role in the repair of DNA double-strand breaks and collapsed replication forks. HR depends on the products of several paralogues of RAD51, including the tetrameric complex of RAD51B, RAD51C, RAD51D and XRCC2 (BCDX2). BCDX2 functions as a mediator of nucleoprotein filament assembly by RAD51 and single-stranded DNA (ssDNA) during HR, but its mechanism remains undefined. Here we report cryogenic electron microscopy reconstructions of human BCDX2 in apo and ssDNA-bound states. The structures reveal how the amino-terminal domains of RAD51B, RAD51C and RAD51D participate in inter-subunit interactions that underpin complex formation and ssDNA-binding specificity. Single-molecule DNA curtain analysis yields insights into how BCDX2 enhances RAD51-ssDNA nucleoprotein filament assembly. Moreover, our cryogenic electron microscopy and functional analyses explain how RAD51C alterations found in patients with cancer inactivate DNA binding and the HR mediator activity of BCDX2. Our findings shed light on the role of BCDX2 in HR and provide a foundation for understanding how pathogenic alterations in BCDX2 impact genome repair.

PubMed: 37344589
DOI: 10.1038/s41586-023-06219-w

Experimental method

ELECTRON MICROSCOPY (3.11 Å)