Mapping DNA repair interactions using EPR and molecular modelling.

了解DNA断裂通过非同源末端连接修复的过程对于开发未来抗癌药物的设计和精确度以及基于CRISPR/Cas9的基因编辑的优化至关重要。X-射线修复交叉互补蛋白4(XRCC4)是一种核心DNA修复因子，因其在这类DNA修复中的重要性而闻名。作为DNA修复过程的一部分，它与其他蛋白质相互作用，包括核心非同源末端连接因子XRCC4样因子(XLF)，它涉及将DNA末端连接在一起促进DNA末端连接，核骨架蛋白中间丝家族孤儿1(IFFO1)，以稳定DNA的断裂末端，以及非同源末端连接连接酶DNA连接酶4(LIG4)，它促进非同源末端连接中的最后连接步骤。XRCC4还与小泛素样修饰物(SUMO)单元链相互作用，实验表明，这一链阻断了其他蛋白质和酶与XRCC4相互作用的位置。通过这种方式，SUMO调节XRCC4的作用和DNA的非同源末端连接。

Understanding the process by which DNA breaks are healed via by non-homologous end joining is vital for developing the design and precision of future anti-cancer medicines and the optimization of CRISPR/Cas9-based gene editing. The X-ray repair cross-complementing protein 4 (XRCC4) is a core DNA repair factor known for its importance in this type of DNA repair. As part of the DNA repair process it interacts with other proteins including the core non-homologous end joining factor XRCC4-like factor (XLF), implicated in tethering the DNA ends together promoting DNA-end ligation, the nucleoskeleton protein intermediate filament family orphan 1 (IFFO1), to stabilise the broken ends of the DNA, and the non-homologous end joining ligating enzyme DNA ligase 4 (LIG4), that facilitates the final ligation step in non-homologous end joining. XRCC4 also interacts with chains of small ubiquitin-like modifier (SUMO) units, which experiments suggest block the sites where the other proteins and enzymes interact with XRCC4. In this way SUMO regulates the action of XRCC4 and the non-homologous end joining of DNA.