DNA-DEPENDENT PROTEIN-KINASE

DNA-dependent protein kinase (DNA-PI) is a nuclear protein serine/thre onine 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 dru gs. In addition, DNA-PK is required to generate the antigen binding si tes of T-cell receptor and immunoglobulin molecules, and the phenotype of the severe combined immunodeficient (scid) mouse is due to a DNA-P K deficiency. Recent data suggest that DNA-PK may also have roles in c ontrolling transcription, apoptosis, and the length of telomeric chrom osomal ends. Finally, DNA-PI( is related to other proteins involved in DNA damage detection, including the protein defective in the human ne urodegenerative and cancer predisposition syndrome ataxia-telangiectas ia. Studies on DNA-PK should provide a better understanding of degener ative diseases and cancer, and may lead to improved therapies for thes e conditions. (C) 1997 Elsevier Science Ltd.