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Regulation of USP7/HAUSP in response to DNA damage: Yet another role for ATM

机译：响应DNA损伤的USP7 / HAUSP调控：ATM的另一个作用

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The ataxia-telangiectasia mutated (ATM) protein kinase is widely accepted to play a key role in the DNA damage response, in particular in the signaling of radiation-induced DNA double-strand breaks. In this regard, ATM activates a number of cell cycle checkpoints to delay DNA replication and ensure the correct processing of the damaged DNA. This is achieved both directly, through phosphorylation of p53 at Serl5, and indirectly, via phosphorylation of Mdm2, Mdmx and Chk2, which subsequently control the cellular levels of the p53 tumor suppressor. Consequently, this causes activation of either a G_1 cell cycle delay, to allow DNA repair processes to be completed before DNA replication, or the initiation of the apoptotic pathway in the case of excessive DNA damage. ATM also plays a key role in the activation of S-phase, as well as G_2/M-phase arrest via phosphorylation of BRCA1, SMC1, FANCD2 and many other substrates (reviewed in ref. 4) and was proved to be activated and thus regulate some of its targets in response to oxidative stress. In total, more than several hundred ATM substrates were identified in global proteome screening in cells subjected to IR, which include a number of transcription factors, proteins that sense and transmit DNA damage signals as well as those that mediate chromatin remodeling, DNA replication, mitosis and other cellular processes.
机译：共济失调-毛细血管扩张突变（ATM）蛋白激酶在DNA损伤反应中，尤其是在辐射诱导的DNA双链断裂的信号传导中起着关键作用。在这方面，ATM激活许多细胞周期检查点以延迟DNA复制并确保对受损DNA的正确处理。这既可以通过Ser15的p53磷酸化直接实现，也可以通过Mdm2，Mdmx和Chk2的磷酸化间接实现，后者随后控制p53肿瘤抑制因子的细胞水平。因此，这会导致G_1细胞周期延迟的激活，从而使DNA修复过程能够在DNA复制之前完成，或者在DNA过度受损的情况下引发凋亡途径。通过BRCA1，SMC1，FANCD2和许多其他底物的磷酸化，ATM在S相活化以及G_2 / M相阻滞中也起着关键作用（参见参考文献4），并被证明是活化的，因此调节其某些目标以响应氧化应激。总体上，在接受IR的细胞中进行全球蛋白质组筛选时，已鉴定出数百种ATM底物，其中包括许多转录因子，感知和传递DNA损伤信号的蛋白质以及介导染色质重塑，DNA复制，有丝分裂的蛋白质。和其他细胞过程。

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