Schlam-Babayov Sapir, Ziv Yael, Shiloh Yosef
The David and Inez Myers Laboratory of Cancer Genetics, Department of Human Molecular Genetics and Biochemistry, Tel Aviv University School of Medicine, Tel Aviv, Israel.
Mol Cell Oncol. 2021 Feb 8;8(2):1881395. doi: 10.1080/23723556.2021.1881395. eCollection 2021.
The DNA damage response is robustly activated by DNA double-strand breaks and controlled by three apical protein kinases of the PI3-kinase-related protein kinase (PIKK) family: ataxia-telangiectasia, mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR) and DNA-dependent protein kinase (DNA-PK). Phosphoproteomic analysis reveals the relative share of these PIKKs in coordinating this network, and compensation by ATR and DNA-PK for ATM absence in the genetic disorder, ataxia-telangiectasia (A-T).
DNA双链断裂可强烈激活DNA损伤反应，该反应由PI3激酶相关蛋白激酶（PIKK）家族的三种顶端蛋白激酶控制：共济失调毛细血管扩张症突变蛋白（ATM）、共济失调毛细血管扩张症和Rad3相关蛋白（ATR）以及DNA依赖性蛋白激酶（DNA-PK）。磷酸化蛋白质组分析揭示了这些PIKK在协调该网络中的相对作用，以及在遗传性疾病共济失调毛细血管扩张症（A-T）中ATR和DNA-PK对ATM缺失的补偿作用。
