据介绍，维持基因组的完整性是一个至关重要且富有挑战性的过程。RAD51重组酶是修复DNA和保护基因组完整性的几个关键过程的核心参与者，在DNA上形成细丝，受到严格调控。其中一种RAD51调节因子是FIGNL1，它在没有DNA损伤和遗传毒性染色质结合时或之后，防止持续的RAD51病灶。
研究人员对FIGNL1与RAD51复合物的冷冻电镜结构研究显示，FIGNL1在FIGNL1六聚体孔中形成非平面六聚体和RAD51 N末端外壳。FIGNL1的孔环或催化残基的突变使其在细丝拆卸中有缺陷，并在小鼠胚胎干细胞中是致命的。
总之，这一研究揭示了一种从结合底物中去除RAD51的独特机制，并为FIGNL1维持基因组稳定性提供了分子基础。
附：英文原文
Title: Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin
Author: Alexander Carver, Tai-Yuan Yu, Luke A. Yates, Travis White, Raymond Wang, Katie Lister, Maria Jasin, Xiaodong Zhang
Issue&Volume: 2024-12-05
Abstract: Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing DNA and protecting genome integrity, forms filaments on DNA, which are tightly regulated. One of these RAD51 regulators is FIGNL1, that prevents persistent RAD51 foci without or after DNA damage and genotoxic chromatin association in cells. The cryogenic electron microscopy structure of FIGNL1 in complex with RAD51 reveals that FIGNL1 forms a non-planar hexamer and RAD51 N terminus enclosure in the FIGNL1 hexamer pore. Mutations in pore loop or catalytic residues of FIGNL1 render it defective in filament disassembly and are lethal in mouse embryonic stem cells. Our study reveals a unique mechanism for removing RAD51 from bound substrates and provides the molecular basis for FIGNL1 in maintaining genome stability.
DOI: adr7920
Source: https://www.science.org/doi/10.1126/science.adr7920