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研究通过XRCC3-RAD51C-RAD51D-XRCC2对RAD51灯丝组装和末端封盖进行低温电镜显示
作者:小柯机器人 发布时间:2025/11/7 14:28:24

英国朗西斯·克里克研究所Stephen C. West课题组开发出用XRCC3-RAD51C-RAD51D-XRCC2观察RAD51灯丝组装和末端封盖的低温电镜显示。这一研究成果发表在2025年11月6日出版的国际学术期刊《科学》上。

在这项工作中,该课题组研究人员发现RAD51类似物组装成两个不同的异四聚物,RAD51B-RAD51C-RAD51D-XRCC2(RAD51B复合物)和XRCC3-RAD51C-RAD51D-XRCC2(XRCC3复合物)。低温电镜显示,RAD51B复合物促进RAD51细丝依赖于三磷酸腺苷水解的动态组装,而XRCC3复合物稳定地盖住RAD51细丝的5'端,促进同源物配对。这些复合物在整个进化过程中高度保守,揭示了DNA修复和复制叉稳定过程中RAD51丝的形成和封盖过程。

研究人员表示,同源重组修复DNA双链断裂并保护停滞的复制叉,但五种RAD51相似物如何参与这些过程尚不清楚。RAD51类似物的突变与遗传性乳腺癌、卵巢癌和易患癌症的范可尼贫血有关。

附:英文原文

Title: Cryo–electron microscopy visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2

Author: Luke A. Greenhough, Lorenzo Galanti, Chih-Chao Liang, Simon J. Boulton, Stephen C. West

Issue&Volume: 2025-11-06

Abstract: Homologous recombination repairs DNA double strand breaks and protects stalled replication forks, but how the five RAD51 paralogs contribute to these processes remains unclear. Mutations in the RAD51 paralogs are linked to heritable breast and ovarian cancers and the cancer-prone disease Fanconi anemia. In this work, we show that the RAD51 paralogs assemble into two distinct heterotetrameric complexes, RAD51B-RAD51C-RAD51D-XRCC2 (RAD51B complex) and XRCC3-RAD51C-RAD51D-XRCC2 (XRCC3 complex). The RAD51B complex promotes dynamic adenosine triphosphate hydrolysis–dependent assembly of RAD51 filaments, whereas the XRCC3 complex stably caps the 5′-termini of RAD51 filaments to promote homologous pairing, as visualized by cryo–electron microscopy. Highly conserved across evolution, these complexes reveal insights into RAD51 filament formation and capping during DNA repair and replication fork stabilization.

DOI: aea1546

Source: https://www.science.org/doi/10.1126/science.aea1546

 

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:63.714