8GJA

RAD51C-XRCC3 structure

8GJA の概要

• エントリーDOI: 10.2210/pdb8gja/pdb
• 分子名称: RAD51C, XRCC3, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: dna-binding dna damage dna repair atp binding, dna binding protein
• 由来する生物種: Alvinella pompejana; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 216210.67

構造登録者

Arvai, A.S.,Tainer, J.A.,Williams, G.,Longo, M.A. (登録日: 2023-03-15, 公開日: 2023-08-16, 最終更新日: 2023-10-18)

主引用文献

Longo, M.A.,Roy, S.,Chen, Y.,Tomaszowski, K.H.,Arvai, A.S.,Pepper, J.T.,Boisvert, R.A.,Kunnimalaiyaan, S.,Keshvani, C.,Schild, D.,Bacolla, A.,Williams, G.J.,Tainer, J.A.,Schlacher, K.
RAD51C-XRCC3 structure and cancer patient mutations define DNA replication roles.
Nat Commun, 14:4445-4445, 2023

PubMed Abstract: RAD51C is an enigmatic predisposition gene for breast, ovarian, and prostate cancer. Currently, missing structural and related functional understanding limits patient mutation interpretation to homology-directed repair (HDR) function analysis. Here we report the RAD51C-XRCC3 (CX3) X-ray co-crystal structure with bound ATP analog and define separable RAD51C replication stability roles informed by its three-dimensional structure, assembly, and unappreciated polymerization motif. Mapping of cancer patient mutations as a functional guide confirms ATP-binding matching RAD51 recombinase, yet highlights distinct CX3 interfaces. Analyses of CRISPR/Cas9-edited human cells with RAD51C mutations combined with single-molecule, single-cell and biophysics measurements uncover discrete CX3 regions for DNA replication fork protection, restart and reversal, accomplished by separable functions in DNA binding and implied 5' RAD51 filament capping. Collective findings establish CX3 as a cancer-relevant replication stress response complex, show how HDR-proficient variants could contribute to tumor development, and identify regions to aid functional testing and classification of cancer mutations.

PubMed: 37488098
DOI: 10.1038/s41467-023-40096-1

実験手法

X-RAY DIFFRACTION (2.6 Å)