DNA-dependent protein kinase catalytic subunit; Ataxia telangiectasia mutated; ATM and Rad3-related kinase (DNA-PKcs; ATM; ATR)

DNA-PKcs, ATM, and ATR are central kinases in the DNA damage response, responsible for detecting DNA lesions and orchestrating repair through phosphorylation of a broad network of substrates. DNA-PKcs primarily mediates nonhomologous end joining of double-strand breaks, ATM is crucial for the homologous recombination pathway and cell cycle checkpoint activation after ionizing radiation, while ATR responds to a wide spectrum of DNA damage including replication stress. Dysfunction or inhibition of these kinases contributes to cancer susceptibility, neurodevelopmental disorders, and can be exploited therapeutically to sensitize cancer cells to cytotoxic therapies[2][3][4][5][7].

Other names

DNA-dependent protein kinase, catalytic subunitPRKDCXRCC7Ataxia telangiectasia mutatedS-T kinase ATMATM- and Rad3-relatedS-T kinase ATR

Inhibition of kinase activity leads to impaired DNA repair, sensitizing cancer cells to chemotherapy and radiotherapy[1][7]. Synthetic lethality: Tumor cells deficient in ATM are reliant on DNA-PKcs; inhibition leads to cell death[5]. Checkpoint abrogation: Inhibiting ATM or ATR can prevent cell cycle arrest in response to DNA damage.