Recruitment of ATR to sites of ionising radiation-induced DNA damage requires ATM and components of the MRN protein complex

被引：117

作者：

Adams, KE ^{[1
]}

Medhurst, AL ^{[1
]}

Dart, DA ^{[1
]}

Lakin, ND ^{[1
]}

机构：

[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England

来源：

ONCOGENE | 2006年 / 25卷 / 28期

关键词：

ataxia telangiectasia mutated and rad3-related (ATR); cell cycle checkpoints; DNA damage and repair;

D O I：

10.1038/sj.onc.1209426

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ATM and ATR are two related kinases essential for signalling DNA damage. Although ATM is thought to be the principle kinase responsible for signalling ionising radiation (IR)-induced DNA damage, ATR also contributes to signalling this form of genotoxic stress. However, the molecular basis of differential ATM and ATR activation in response to IR remains unclear. Here, we report that ATR is recruited to sites of IR-induced DNA damage significantly later than activation of ATM. We show that ATR is recruited to IR-induced nuclear foci in G(1) and S phase of the cell cycle, supporting a role for ATR in detecting DNA damage outside of S phase. In addition, we report that recruitment of ATR to sites of IR-induced DNA damage is concomitant with appearance of large tracts of single-stranded DNA (ssDNA) and that this event is dependent on ATM and components of the Mre11/Rad50/Nbs1 (MRN) protein complex.

引用

页码：3894 / 3904

页数：11

共 61 条

[1] Cell cycle checkpoint signaling through the ATM and ATR kinases [J].