Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
Curr Opin Struct Biol. 2023 Oct;82:102651. doi: 10.1016/j.sbi.2023.102651. Epub 2023 Jul 10.
Members of the phosphatidylinositol 3' kinase (PI3K)-related kinases (PIKKs) family, including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), ataxia telangiectasia mutated (ATM), ataxia-telangiectasia mutated and Rad3-related (ATR), mammalian target of rapamycin (mTOR), suppressor with morphological effect on genitalia 1 (SMG1), and transformation/transcription domain-associated protein 1 (TRRAP/Tra1), participate in a variety of physiological processes, such as cell-cycle control, metabolism, transcription, replication, and the DNA damage response. In eukaryotic cells, DNA-PKcs, ATM, and ATR-ATRIP are the main sensors and regulators of DNA double-strand break repair. The purpose of this review is to describe recent structures of DNA-PKcs, ATM, and ATR, as well as their functions in activation and phosphorylation in different DNA repair pathways.
PI3K 相关激酶（PIKKs）家族成员，包括 DNA 依赖性蛋白激酶催化亚基（DNA-PKcs）、共济失调毛细血管扩张突变（ATM）、共济失调毛细血管扩张突变和 Rad3 相关（ATR）、雷帕霉素靶蛋白（mTOR）、生殖器形态效应抑制物 1（SMG1）和转化/转录域相关蛋白 1（TRRAP/Tra1），参与多种生理过程，如细胞周期控制、代谢、转录、复制和 DNA 损伤反应。在真核细胞中，DNA-PKcs、ATM 和 ATR-ATRIP 是 DNA 双链断裂修复的主要传感器和调节剂。本综述的目的是描述 DNA-PKcs、ATM 和 ATR 的最新结构及其在不同 DNA 修复途径中的激活和磷酸化功能。
