DNA-dependent protein kinase

DNA-dependent protein kinase (DNA-PI) is a nuclear protein serine/threonine kinase that is activated by DNA double strand breaks (DSBs). It is a component of the DNA DSB repair apparatus, and cells deficient in DNA-PK are hypersensitive to ionising radiation and radio-mimetic drugs. In addition, DNA-PK is required to generate the antigen binding sites of T-cell receptor and immunoglobulin molecules, and the phenotype of the severe combined immunodeficient (scid) mouse is due to a DNA-PK deficiency. Recent data suggest that DNA-PK may also have roles in controlling transcription, apoptosis, and the length of telomeric chromosomal ends. Finally, DNA-PI( is related to other proteins involved in DNA damage detection, including the protein defective in the human neurodegenerative and cancer predisposition syndrome ataxia-telangiectasia. Studies on DNA-PK should provide a better understanding of degenerative diseases and cancer, and may lead to improved therapies for these conditions. (C) 1997 Elsevier Science Ltd.