Institute for Research in Biomedicine Barcelona, C/ Baldiri Reixac 10, 08028 Barcelona, Spain.
Nat Rev Mol Cell Biol. 2011 Feb;12(2):90-103. doi: 10.1038/nrm3047.
The maintenance of genome stability depends on the DNA damage response (DDR), which is a functional network comprising signal transduction, cell cycle regulation and DNA repair. The metabolism of DNA double-strand breaks governed by the DDR is important for preventing genomic alterations and sporadic cancers, and hereditary defects in this response cause debilitating human pathologies, including developmental defects and cancer. The MRE11 complex, composed of the meiotic recombination 11 (MRE11), RAD50 and Nijmegen breakage syndrome 1 (NBS1; also known as nibrin) proteins is central to the DDR, and recent insights into its structure and function have been gained from in vitro structural analysis and studies of animal models in which the DDR response is deficient.
基因组稳定性的维持依赖于 DNA 损伤反应 (DDR),这是一个由信号转导、细胞周期调控和 DNA 修复组成的功能网络。DDR 调控的 DNA 双链断裂的代谢对于防止基因组改变和散发性癌症很重要,而该反应的遗传缺陷会导致使人衰弱的人类病理,包括发育缺陷和癌症。MRE11 复合物由减数分裂重组 11 (MRE11)、RAD50 和 Nijmegen 断裂综合征 1 (NBS1;也称为 nibrin) 蛋白组成,是 DDR 的核心,最近通过体外结构分析和 DDR 反应缺陷的动物模型研究获得了对其结构和功能的深入了解。