DNA损伤反应中的ATM信号传导与基因组稳定性

ATM signaling and genomic stability in response to DNA damage.

作者信息

Lavin Martin F, Birrell Geoff, Chen Philip, Kozlov Sergei, Scott Shaun, Gueven Nuri

机构信息

Queensland Cancer Fund Research Unit, The Queensland Institute of Medical Research, PO Box Royal Brisbane Hospital, Herston, Brisbane 4029, Australia.

出版信息

Mutat Res. 2005 Jan 6;569(1-2):123-32. doi: 10.1016/j.mrfmmm.2004.04.020.

DOI:10.1016/j.mrfmmm.2004.04.020

PMID:15603757

Abstract

DNA double strand breaks represent the most threatening lesion to the integrity of the genome in cells exposed to ionizing radiation and radiomimetic chemicals. Those breaks are recognized, signaled to cell cycle checkpoints and repaired by protein complexes. The product of the gene (ATM) mutated in the human genetic disorder ataxia-telangiectasia (A-T) plays a central role in the recognition and signaling of DNA damage. ATM is one of an ever growing number of proteins which when mutated compromise the stability of the genome and predispose to tumour development. Mechanisms for recognising double strand breaks in DNA, maintaining genome stability and minimizing risk of cancer are discussed.

摘要

DNA双链断裂是暴露于电离辐射和放射模拟化学物质的细胞中基因组完整性面临的最具威胁性的损伤。这些断裂会被识别，传递信号至细胞周期检查点，并由蛋白质复合物进行修复。在人类遗传性共济失调毛细血管扩张症（A-T）中发生突变的基因（ATM）的产物，在DNA损伤的识别和信号传递中起核心作用。ATM是越来越多的蛋白质之一，这些蛋白质发生突变时会损害基因组的稳定性并易引发肿瘤发展。本文讨论了识别DNA双链断裂、维持基因组稳定性以及将癌症风险降至最低的机制。