DNA-PKcs: A Multi-Faceted Player in DNA Damage Response.
DNA-PKcs: A Multi-Faceted Player in DNA Damage Response.
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DNA-PKcs：DNA 损伤反应中的多面角色
DOI：
10.3389/fgene.2020.607428
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发表时间：
2020
影响因子：
3.7
通讯作者：
Zhou PK
中科院分区：
文献类型：
--
作者：
Yue X;Bai C;Xie D;Ma T;Zhou PK
dna依赖性蛋白激酶催化亚基（DNA-PKcs）是磷脂酰肌醇3-激酶相关激酶家族的成员，可磷酸化700多种底物。DNA- pkcs作为核心酶，与Ku80/Ku70异源二聚体组成活性DNA- pk全酶，在细胞DNA损伤应答（DDR）中发挥重要作用。一旦DNA双链断裂（dsb）在细胞中发生，DNA- pkcs被迅速招募到损伤部位并被激活。DNA-PKcs被自身磷酸化和被ataxia -毛细血管扩张症多位点突变磷酸化，并磷酸化其他靶点，参与一系列DDR和修复过程，决定细胞命运：DSBs NHEJ修复和途径选择、复制应激反应、细胞周期点、端粒长度维持、衰老、自噬等。由于DNA- pkcs在细胞对DNA损伤的反应中具有特殊和多方面的作用，因此精确调控其功能复合物的形成、动态和活性对于保护基因组稳定具有重要意义。另一方面，靶向DNA-PKcs已被认为是探索新型放射增敏剂和癌细胞杀伤剂的一种有前途的策略。DNA-PKcs抑制剂联合放疗可有效提高放疗疗效，为癌症治疗提供更多可能性。
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a member of the phosphatidylinositol 3-kinase related kinase family, which can phosphorylate more than 700 substrates. As the core enzyme, DNA-PKcs forms the active DNA-PK holoenzyme with the Ku80/Ku70 heterodimer to play crucial roles in cellular DNA damage response (DDR). Once DNA double strand breaks (DSBs) occur in the cells, DNA-PKcs is promptly recruited into damage sites and activated. DNA-PKcs is auto-phosphorylated and phosphorylated by Ataxia-Telangiectasia Mutated at multiple sites, and phosphorylates other targets, participating in a series of DDR and repair processes, which determine the cells’ fates: DSBs NHEJ repair and pathway choice, replication stress response, cell cycle checkpoints, telomeres length maintenance, senescence, autophagy, etc. Due to the special and multi-faceted roles of DNA-PKcs in the cellular responses to DNA damage, it is important to precisely regulate the formation and dynamic of its functional complex and activities for guarding genomic stability. On the other hand, targeting DNA-PKcs has been considered as a promising strategy of exploring novel radiosensitizers and killing agents of cancer cells. Combining DNA-PKcs inhibitors with radiotherapy can effectively enhance the efficacy of radiotherapy, offering more possibilities for cancer therapy.
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影响因子：
19
作者：
Ceccaldi R;Rondinelli B;D'Andrea AD
通讯作者：
D'Andrea AD
影响因子：
4.8
作者：
Chen, Benjamin P. C.;Uematsu, Naoya;Chen, David J.
通讯作者：
Chen, David J.
影响因子：
16
作者：
Buisson R;Boisvert JL;Benes CH;Zou L
通讯作者：
Zou L
影响因子：
3.6
作者：
Baskar R;Lee KA;Yeo R;Yeoh KW
通讯作者：
Yeoh KW
影响因子：
5.3
作者：
Ding, Q;Reddy, YVR;Meek, K
通讯作者：
Meek, K