C1orf112 与 FIGNL1 合作，促进 RAD51 丝的解体和 DNA 链间交联修复。
C1orf112 teams up with FIGNL1 to facilitate RAD51 filament disassembly and DNA interstrand cross-link repair.
机构信息
Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
出版信息
Cell Rep. 2023 Aug 29;42(8):112907. doi: 10.1016/j.celrep.2023.112907. Epub 2023 Jul 28.
The recombinase RAD51 plays a core role in DNA repair by homologous recombination (HR). The assembly and disassembly of RAD51 filament need to be orderly regulated by mediators such as BRCA2 and anti-recombinases. To screen for potential regulators of RAD51, we perform RAD51 proximity proteomics and identify factor C1orf112. We further find that C1orf112 complexed with FIGNL1 facilitates RAD51 filament disassembly in the HR step of Fanconi anemia (FA) pathway. Specifically, C1orf112 physically interacts with FIGNL1 and enhances its protein stability. Meanwhile, the RAD51 filament disassembly activity of FIGNL1 is directly stimulated by C1orf112. BRCA2 directly interacts with C1orf112-FIGNL1 complex and functions upstream of this complex to protect RAD51 filament from premature disassembly. C1orf112- and FIGNL1-deficient cells are primarily sensitive to DNA interstrand cross-link (ICL) agents. Thus, these findings suggest an important function of C1orf112 in RAD51 regulation in the HR step of ICL repair by FA pathway.
重组酶 RAD51 在同源重组 (HR) 介导的 DNA 修复中发挥核心作用。RAD51 丝的组装和拆卸需要 BRCA2 和抗重组酶等介质进行有序调节。为了筛选 RAD51 的潜在调节剂，我们进行 RAD51 邻近蛋白质组学分析，鉴定出因子 C1orf112。我们进一步发现 C1orf112 与 FIGNL1 复合物促进 FA 通路中 HR 步骤 RAD51 丝的解体。具体而言，C1orf112 与 FIGNL1 相互作用，并增强其蛋白质稳定性。同时，C1orf112 直接刺激 FIGNL1 的 RAD51 丝解体活性。BRCA2 与 C1orf112-FIGNL1 复合物直接相互作用，并在上游发挥作用，保护 RAD51 丝免于过早解体。C1orf112 和 FIGNL1 缺陷细胞对 DNA 链间交联 (ICL) 剂主要敏感。因此，这些发现表明 C1orf112 在 FA 通路 ICL 修复的 HR 步骤中 RAD51 调节中的重要功能。
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