Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy.
Int J Mol Sci. 2023 Aug 3;24(15):12377. doi: 10.3390/ijms241512377.
DNA double-strand breaks (DSBs) are a significant threat to cell viability due to the induction of genome instability and the potential loss of genetic information. One of the key players for early DNA damage response is the conserved Mre11/Rad50 Nbs1/Xrs2 (MRN/X) complex, which is quickly recruited to the DNA's ruptured ends and is required for their tethering and their subsequent repair via different pathways. The MRN/X complex associates with several other proteins to exert its functions, but it also exploits sophisticated internal dynamic properties to orchestrate the several steps required to address the damage. In this review, we summarize the intrinsic molecular features of the MRN/X complex through biophysical, structural, and computational analyses in order to describe the conformational transitions that allow for this complex to accomplish its multiple functions.
DNA 双链断裂（DSBs）是对细胞活力的重大威胁，因为它会导致基因组不稳定和潜在的遗传信息丢失。在早期 DNA 损伤反应中，一个关键的参与者是保守的 Mre11/Rad50 Nbs1/Xrs2（MRN/X）复合物，它迅速被招募到 DNA 的断裂末端，并通过不同的途径需要其连接和随后的修复。MRN/X 复合物与其他几种蛋白质结合以发挥其功能，但它也利用复杂的内部动态特性来协调完成修复所需的几个步骤。在这篇综述中，我们通过生物物理、结构和计算分析总结了 MRN/X 复合物的内在分子特征，以描述允许该复合物完成其多种功能的构象转变。
