前 rRNA 有助于 RAD51AP1 招募到 DNA 双链断裂处。

Pre-rRNA facilitates the recruitment of RAD51AP1 to DNA double-strand breaks.

机构信息

School of Life Sciences, Fudan University, Shanghai, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.

School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang Province, China.

出版信息

J Biol Chem. 2024 Mar;300(3):107115. doi: 10.1016/j.jbc.2024.107115. Epub 2024 Feb 24.

DOI:10.1016/j.jbc.2024.107115

PMID:38403248

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10959706/

Abstract

RAD51-associated protein 1 (RAD51AP1) is known to promote homologous recombination (HR) repair. However, the precise mechanism of RAD51AP1 in HR repair is unclear. Here, we identify that RAD51AP1 associates with pre-rRNA. Both the N terminus and C terminus of RAD51AP1 recognize pre-rRNA. Pre-rRNA not only colocalizes with RAD51AP1 at double-strand breaks (DSBs) but also facilitates the recruitment of RAD51AP1 to DSBs. Consistently, transient inhibition of pre-rRNA synthesis by RNA polymerase I inhibitor suppresses the recruitment of RAD51AP1 as well as HR repair. Moreover, RAD51AP1 forms liquid-liquid phase separation in the presence of pre-rRNA in vitro, which may be the molecular mechanism of RAD51AP1 foci formation. Taken together, our results demonstrate that pre-rRNA mediates the relocation of RAD51AP1 to DSBs for HR repair.

摘要

RAD51 相关蛋白 1（RAD51AP1）已知可促进同源重组（HR）修复。然而，RAD51AP1 在 HR 修复中的精确机制尚不清楚。在这里，我们发现 RAD51AP1 与前 rRNA 相关联。RAD51AP1 的 N 端和 C 端都识别前 rRNA。前 rRNA 不仅与 RAD51AP1 在双链断裂（DSB）处共定位，而且还促进 RAD51AP1 向 DSB 的募集。一致地，通过 RNA 聚合酶 I 抑制剂瞬时抑制前 rRNA 的合成会抑制 RAD51AP1 的募集以及 HR 修复。此外，RAD51AP1 在存在前 rRNA 的情况下在体外形成液-液相分离，这可能是 RAD51AP1 焦点形成的分子机制。总之，我们的结果表明，前 rRNA 将 RAD51AP1 重新定位到 DSB 以进行 HR 修复。