Chromosomes are constantly damaged by exogenous and endogenous factors. To cope with DNA damage, eukaryotic cells are equipped with three phosphatidylinositol 3-kinase-related kinases (PIKKs), such as ATM, ATR, and DNA-PK. PIKKs are structurally related to phosphatidylinositol 3-kinase (lipid kinase), however possess protein kinase activities. The Mre11-Rad50-Nbs1 and the Ku complex interact with and activate ATM and DNA-PKcs at double-stranded DNA breaks (DSBs), respectively. In contrast, ATR responds to various types of DNA lesions by interacting with replication protein A (RPA)-covered single-stranded DNA (ssDNA). Several lines of evidence have established a model in which ATR is activated by interacting with ATR activating proteins including TopBP1 and ETAA1 at DNA lesions in humans, yet the interaction of ATR with RPA-covered ssDNA does not result in ATR activation. In budding yeast, the Mec1-Ddc2 complex (Mec1-Ddc2) corresponds to ATR-ATRIP. Similar to ATR, Mec1 activation is accomplished by interactions with Mec1 activating proteins, which are Ddc1, Dpb11 (TopBP1 homolog) and Dna2. However, recent studies provide results supporting the idea that Mec1ATR is also activated by interacting with RPA-covered ssDNA tracts. These observations suggest that all the ATM, ATR, DNA-PK family proteins can be activated immediately upon DNA damage recognition.

中文翻译：

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DNA损伤识别后激活ATR相关蛋白激酶。

染色体经常受到外源性和内源性因素的破坏。为了应对DNA损伤，真核细胞配备了三种磷脂酰肌醇3激酶相关激酶（PIKK），例如ATM，ATR和DNA-PK。PIKK在结构上与磷脂酰肌醇3激酶（脂质激酶）有关，但具有蛋白激酶活性。Mre11-Rad50-Nbs1和Ku复合物分别与双链DNA断裂（DSB）相互作用并激活ATM和DNA-PKcs。相反，ATR通过与复制蛋白A（RPA）覆盖的单链DNA（ssDNA）相互作用来响应各种类型的DNA损伤。有几条证据建立了一个模型，其中ATR通过与人类DNA损伤处的ATR激活蛋白（包括TopBP1和​​ETAA1）相互作用而被激活，但是ATR与RPA覆盖的ssDNA的相互作用不会导致ATR激活。在发芽酵母中，Mec1-Ddc2复合物（Mec1-Ddc2）对应于ATR-ATRIP。与ATR相似，Mec1激活是通过与Mec1激活蛋白（Ddc1，Dpb11（TopBP1同源物）和Dna2）相互作用来完成的。但是，最近的研究提供了支持以下观点的结果：Mec1ATR也可通过与RPA覆盖的ssDNA束相互作用而被激活。这些观察结果表明，一旦识别出DNA损伤，即可立即激活所有ATM，ATR，DNA-PK家族蛋白。最近的研究提供了支持以下想法的结果，即Mec1ATR也可以通过与RPA覆盖的ssDNA片段相互作用而被激活。这些观察结果表明，一旦识别出DNA损伤，即可立即激活所有ATM，ATR，DNA-PK家族蛋白。最近的研究提供了支持以下想法的结果，即Mec1ATR也可以通过与RPA覆盖的ssDNA束相互作用而被激活。这些观察结果表明，一旦识别出DNA损伤，即可立即激活所有ATM，ATR，DNA-PK家族蛋白。