DNA double-strand breaks (DSBs) can be repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR). HR is initiated by nucleolytic degradation of the DSB ends in a process termed resection. The Mre11-Rad50-Xrs2/NBS1 (MRX/N) complex is a multifunctional enzyme that, aided by the Sae2/CtIP protein, promotes DSB resection and maintains the DSB ends tethered to each other to facilitate their re-ligation. Furthermore, it activates the protein kinase Tel1/ATM, which initiates DSB signaling. In Saccharomyces cerevisiae, these MRX functions are inhibited by the Rif2 protein, which is enriched at telomeres and protects telomeric DNA from being sensed and processed as a DSB. The present review focuses on recent data showing that Sae2 and Rif2 regulate MRX functions in opposite manners by interacting with Rad50 and influencing ATP-dependent Mre11-Rad50 conformational changes. As Sae2 is enriched at DSBs whereas Rif2 is predominantly present at telomeres, the relative abundance of these two MRX regulators can provide an effective mechanism to activate or inactivate MRX depending on the nature of chromosome ends.

DNA 双链断裂 (DSB) 可以通过非同源末端连接 (NHEJ) 或同源重组 (HR) 进行修复。HR 是由 DSB 在称为切除的过程中的核解降解开始的。Mre11-Rad50-Xrs2/NBS1 (MRX/N) 复合物是一种多功能酶，在 Sae2/CtIP 蛋白的帮助下，促进 DSB 切除并保持 DSB 末端相互连接以促进它们的重新连接。此外，它还能激活启动 DSB 信号传导的蛋白激酶 Tel1/ATM。在酿酒酵母中，这些 MRX 功能被 Rif2 蛋白抑制，该蛋白在端粒富集并保护端粒 DNA 不被感知和作为 DSB 处理。本综述重点关注最近的数据，表明 Sae2 和 Rif2 通过与 Rad50 相互作用并影响 ATP 依赖性 Mre11-Rad50 构象变化以相反的方式调节 MRX 功能。由于 Sae2 在 DSB 处富集，而 Rif2 主要存在于端粒，这两种 MRX 调节剂的相对丰度可以提供一种有效的机制来激活或灭活 MRX，具体取决于染色体末端的性质。