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Philos Trans R Soc Lond B Biol Sci. 1996 Feb 29;351(1336):173-9.

DNA-dependent protein kinase defects are linked to deficiencies in DNA repair and V(D)J recombination.

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Wellcome/CRC Institute, Cambridge, U.K.


DNA-dependent protein kinase is a nuclear serine/threonine kinase whose catalytic properties are expressed only when the enzyme is bound to DNA ends or other discontinuities in the DNA. DNA-PK comprises two components: one mediates binding to DNA and corresponds to the heterodimeric human autoimmune antigen Ku; the other, DNA-PK catalytic subunit (DNA-PKcs), is a polypeptide of approximately 450 kDa. DNA-PK deficiencies are associated with certain mutant rodent cell lines that display defects in DNA double strand break repair and V(D)J recombination. Specifically, hamster xrs-6 cells lack Ku function, whereas murine scid and hamster V3 cells lack functional DNA-PKcs. Furthermore, the phenotypes of xrs-6 and V3 cells can be corrected by the expression of the genes encoding the 80 kDa component of Ku or DNA-PKcs, respectively. These results imply that DNA-PK is an important component of the DNA double strand break repair/recombination apparatus. Possible roles for DNA-PK in these processes are discussed.

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