RAD52双环重塑复制叉，限制叉反转，这一成果由爱荷华大学卡佛医学院Maria Spies研究组经过不懈努力而取得。相关论文于2025年4月2日发表在《自然》杂志上。

通过P1核酸酶敏感性、生化和单分子分析，该课题组研究人员发现RAD52通过其链交换活性动态地重塑复制叉。叉上单链DNA结合蛋白RPA的存在调节了链交换的动力学，而不妨碍反应结果。质谱和单粒子低温电镜显示，复制叉促进了一种独特的核蛋白结构，其中包含两个非美RAD52环的头对头排列，其延伸的带正电的表面可容纳复制叉的所有三个臂。课题组认为该表面的形成和连续性对链交换反应和与SMARCAL1的竞争很重要。

研究人员表示，人类RAD52是一种多功能DNA修复蛋白，参与多种支持基因组稳定性的细胞事件，包括保护停滞的DNA复制叉免受过度降解。在它的看门人角色中，RAD52在复制压力期间结合并稳定停滞的复制分叉，保护它们免受SMARCAL1马达的逆转。RAD52介导的分叉保护的结构和分子机制尚不清楚。

附：英文原文

Title: The RAD52 double-ring remodels replication forks restricting fork reversal

Author: Honda, Masayoshi, Razzaghi, Mortezaali, Gaur, Paras, Malacaria, Eva, Marozzi, Giorgia, Di Biagi, Ludovica, Aiello, Francesca Antonella, Paintsil, Emeleeta A., Stanfield, Andrew J., Deppe, Bailey J., Gakhar, Lokesh, Schnicker, Nicholas J., Spies, M. Ashley, Pichierri, Pietro, Spies, Maria

Issue&Volume: 2025-04-02

Abstract: Human RAD52 is a multifunctional DNA repair protein involved in several cellular events that support genome stability, including protection of stalled DNA replication forks from excessive degradation1,2,3,4. In its gatekeeper role, RAD52 binds to and stabilizes stalled replication forks during replication stress, protecting them from reversal by SMARCAL1 motor3. The structural and molecular mechanism of the RAD52-mediated fork protection remains elusive. Here, using P1 nuclease sensitivity, biochemical and single-molecule analyses, we show that RAD52 dynamically remodels replication forks through its strand exchange activity. The presence of the single-stranded DNA binding protein RPA at the fork modulates the kinetics of the strand exchange without impeding the reaction outcome. Mass photometry and single-particle cryo-electron microscopy show that the replication fork promotes a unique nucleoprotein structure containing head-to-head arrangement of two undecameric RAD52 rings with an extended positively charged surface that accommodates all three arms of the replication fork. We propose that the formation and continuity of this surface is important for the strand exchange reaction and for competition with SMARCAL1.

DOI: 10.1038/s41586-025-08753-1

Source: https://www.nature.com/articles/s41586-025-08753-1