Regulation of the DNA-dependent protein kinase (DNA-PK) activity in eukaryotic cells

The DNA-dependent protein kinase (DNA-PK) is a trimeric nuclear serine/thre onine protein kinase consisting of a large catalytic sub-unit and the Ku he terodimer that regulates kinase activity by its association with DNA. DNA-P K is a major component of the DNA double strand break repair apparatus, and cells deficient in one of its component are hypersensitive to ionizing rad iation. DNA-PK is also required to lymphoid V(D)J recombination and its abs ence confers in mice a severe combined immunodeficiency phenotype. The purp ose of this review is to summarize the current knowledge on the mechanisms that contribute to regulate DNA-PK activity in vivo or in vitro and relates them to the role of DNA-PK in cellular functions. Finally, the studies dev oted to drug-inhibition of DNA-PK in order to enhance cancer therapy by DNA -damaging agents are presented. (C) Societe francaise de biochimie et biolo gie moleculaire / Elsevier, Paris.