DNA-DEPENDENT PROTEIN-KINASE DEFECTS ARE LINKED TO DEFICIENCIES IN DNA-REPAIR AND V(D)J RECOMBINATION

DNA-dependent protein kinase is a nuclear serine/threonine kinase whos e catalytic properties are expressed only when the enzyme is bound to DNA ends or other discontinuities in the DNA. DNA-PK comprises two com ponents: one mediates binding to DNA and corresponds to the heterodime ric human autoimmune antigen Ku; the other, DNA-PK catalytic subunit ( DNA-PKes), is a polypeptide of approximately 450 kDa. DNA-PR deficienc ies are associated with certain mutant rodent cell lines that display defects in DNA double strand break repair and V(D)J recombination. Spe cifically, hamster xrs-6 cells lack Ku function, whereas murine scid a nd hamster V3 cells lack functional DNA-PKes. Furthermore, the phenoty pes of xrs-6 and V3 cells can be corrected by the expression of the ge nes encoding the 80 kDa component of Ku or DNA-PKes, respectively. The se results imply that DNA-PK is an important component of the DNA doub le strand break repair/recombination apparatus. Possible roles for DNA -PK in these processes are discussed.