8RCF

RAD51 nucleoprotein filament on double-stranded abasic DNA

8RCF の概要

• エントリーDOI: 10.2210/pdb8rcf/pdb
• 関連するPDBエントリー: 8RCD
• EMDBエントリー: 19051
• 分子名称: DNA repair protein RAD51 homolog 1, DNA (5'-D(P*TP*GP*(3DR)P*TP*GP*(3DR)P*TP*GP*(3DR)P*TP*GP*(3DR)P*TP*GP*(3DR)P*TP*GP*(3DR)P*TP*GP*(3DR)P*TP*G)-3'), DNA (5'-D(P*CP*AP*CP*CP*AP*CP*CP*AP*CP*CP*AP*CP*CP*AP*CP*CP*AP*CP*CP*AP*CP*CP*A)-3'), ... (5 entities in total)
• 機能のキーワード: homologous recombination, dna replication, abasic dna, dna binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 313853.02

構造登録者

Appleby, R.,Pellegrini, L. (登録日: 2023-12-06, 公開日: 2024-09-04, 最終更新日: 2025-05-21)

主引用文献

Hanthi, Y.W.,Ramirez-Otero, M.A.,Appleby, R.,De Antoni, A.,Joudeh, L.,Sannino, V.,Waked, S.,Ardizzoia, A.,Barra, V.,Fachinetti, D.,Pellegrini, L.,Costanzo, V.
RAD51 protects abasic sites to prevent replication fork breakage.
Mol.Cell, 84:3026-3043.e11, 2024

PubMed Abstract: Abasic sites are DNA lesions repaired by base excision repair. Cleavage of unrepaired abasic sites in single-stranded DNA (ssDNA) can lead to chromosomal breakage during DNA replication. How rupture of abasic DNA is prevented remains poorly understood. Here, using cryoelectron microscopy (cryo-EM), Xenopus laevis egg extracts, and human cells, we show that RAD51 nucleofilaments specifically recognize and protect abasic sites, which increase RAD51 association rate to DNA. In the absence of BRCA2 or RAD51, abasic sites accumulate as a result of DNA base methylation, oxidation, and deamination, inducing abasic ssDNA gaps that make replicating DNA fibers sensitive to APE1. RAD51 assembled on abasic DNA prevents abasic site cleavage by the MRE11-RAD50 complex, suppressing replication fork breakage triggered by an excess of abasic sites or POLθ polymerase inhibition. Our study highlights the critical role of BRCA2 and RAD51 in safeguarding against unrepaired abasic sites in DNA templates stemming from base alterations, ensuring genomic stability.

PubMed: 39178838
DOI: 10.1016/j.molcel.2024.07.004

実験手法

ELECTRON MICROSCOPY (3.4 Å)