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 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.
Finnie
N J
NJ
Wellcome/CRC Institute, Cambridge, U.K.
Gottlieb
T M
TM
Blunt
T
T
Jeggo
P A
PA
Jackson
S P
SP
D000818:Animals; D004254:DNA Nucleotidyltransferases / Q000235:genetics*; D004260:DNA Repair / Q000502:physiology*; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D015329:Gene Rearrangement, T-Lymphocyte / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases