Activation of ATM and Chk2 kinases in relation to the amount of DNA strand breaks
Activation of ATM and Chk2 kinases in relation to the amount of DNA strand breaks
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DOI：
10.1038/sj.onc.1207986
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发表时间：
2004-10-07
期刊：
影响因子：
8
通讯作者：
Delia, D
中科院分区：
文献类型：
--
作者：
Buscemi, G;Perego, P;Delia, D
对DNA损伤的不同检查点反应可能反映了损伤信号网络分子组分对病变类型和数量的不同敏感性。在这里，我们确定了检查点激酶ATM和Chk2 （ATM的后一底物）的激活动力学与基因组DNA单链（SSBs）和双链断裂（DSBs）初始产量的关系。我们发现，低至0.25 Gy的γ辐射（IR）剂量会产生大量的ssb，但每个细胞只产生少量的dsb（每个细胞19个dsb（例如1 Gy）），导致Thr387上Chk2的自磷酸化，Chk2依赖性p21（waf1）的积累和S期检查点阻滞。我们的研究结果表明，与ATM相反，Chk2活性由更多的dsb触发，这意味着，低于一定阈值水平的病变(
The diverse checkpoint responses to DNA damage may reflect differential sensitivities by molecular components of the damage-signalling network to the type and amount of lesions. Here, we determined the kinetics of activation of the checkpoint kinases ATM and Chk2 ( the latter substrate of ATM) in relation to the initial yield of genomic DNA single-strand (SSBs) and double-strand breaks (DSBs). We show that doses of gamma-radiation (IR) as low as 0.25 Gy, which generate vast numbers of SSBs but only a few DSBs per cell (19 DSBs per cell (e.g. 1 Gy), which cause Chk2 autophosphorylation on Thr387, Chk2-dependent accumulation of p21(waf1) and checkpoint arrest in the S phase. Our results indicate that, in contrast to ATM, Chk2 activity is triggered by a greater number of DSBs, implying that, below a certain threshold level of lesions (