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-Structure paper
タイトル | RAD51 protects abasic sites to prevent replication fork breakage. |
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ジャーナル・号・ページ | Mol Cell, Vol. 84, Issue 16, Page 3026-3043.e11, Year 2024 |
掲載日 | 2024年8月22日 |
著者 | Yodhara Wijesekara Hanthi / Miguel Angel Ramirez-Otero / Robert Appleby / Anna De Antoni / Luay Joudeh / Vincenzo Sannino / Salli Waked / Alessandra Ardizzoia / Viviana Barra / Daniele Fachinetti / Luca Pellegrini / Vincenzo Costanzo / |
PubMed 要旨 | 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 ...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. |
リンク | Mol Cell / PubMed:39178838 |
手法 | EM (らせん対称) |
解像度 | 3.2 - 3.4 Å |
構造データ | EMDB-19050, PDB-8rcd: EMDB-19051, PDB-8rcf: |
化合物 | ChemComp-ATP: ChemComp-CA: |
由来 |
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キーワード | DNA BINDING PROTEIN / Homologous recombination / DNA replication / abasic DNA |