8FAZ

Cryo-EM structure of the human BCDX2 complex

8FAZ の概要

• エントリーDOI: 10.2210/pdb8faz/pdb
• EMDBエントリー: 28961
• 分子名称: DNA repair protein RAD51 homolog 2, DNA repair protein RAD51 homolog 3, DNA repair protein RAD51 homolog 4, ... (7 entities in total)
• 機能のキーワード: dna binding protein, atp binding domain, homologous recombination, rad51 paralog, recombination
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 150935.41

構造登録者

Jia, L.,Wasmuth, E.V.,Ruben, E.A.,Sung, P.,Rawal, Y.,Greene, E.C.,Meir, A.,Olsen, S.K. (登録日: 2022-11-29, 公開日: 2023-06-21, 最終更新日: 2025-05-28)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.3 Å)