ATM and the Mre11 complex combine to recognize and signal DNA double-strand breaks

被引:0
作者
M F Lavin
机构
[1] Radiation Biology and Oncology Laboratory,
[2] Queensland Institute of Medical Research,undefined
[3] Faculty of Health Sciences,undefined
[4] University of Queensland,undefined
来源
Oncogene | 2007年 / 26卷
关键词
ATM; Mre11 complex; DNA double strand breaks; signal transduction; functional consequences;
D O I
暂无
中图分类号
学科分类号
摘要
The recognition and repair of DNA double-strand breaks (DSBs) is a complex process that draws upon a multitude of proteins. This is not surprising since this is a lethal lesion if left unrepaired and also contributes to genome instability and the consequential risk of cancer and other pathologies. Some of the key proteins that recognize these breaks in DNA are mutated in distinct genetic disorders that predispose to agent sensitivity, genome instability, cancer predisposition and/or neurodegeneration. These include members of the Mre11 complex (Mre11/Rad50/Nbs1) and ataxia-telangiectasia (A-T) mutated (ATM), mutated in the human genetic disorder A-T. The mre11 (MRN) complex appears to be the major sensor of the breaks and subsequently recruits ATM where it is activated to phosphorylate in turn members of that complex and a variety of other proteins involved in cell-cycle control and DNA repair. The MRN complex is also upstream of ATM and ATR (A-T-mutated and rad3-related) protein in responding to agents that block DNA replication. To date, more than 30 ATM-dependent substrates have been identified in multiple pathways that maintain genome stability and reduce the risk of disease. We focus here on the relationship between ATM and the MRN complex in recognizing and responding to DNA DSBs.
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页码:7749 / 7758
页数:9
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