Role of DNA-PK in the cellular response to DNA double-strand breaks.
The DNA-dependent protein kinase (DNA-PK) plays a critical role in DNA double-strand break (DSB) repair and in V(D)J recombination. DNA-PK also plays a very important role in triggering apoptosis in response to severe DNA damage or critically shortened telomeres. Paradoxically, components of the DNA-PK complex are present at the mammalian telomere where they function in capping chromosome ends to prevent them from being mistaken for double-strand breaks. In addition, DNA-PK appears to be involved in mounting an innate immune response to bacterial DNA and to viral infection. As DNA-PK localizes very rapidly to DNA breaks and phosphorylates itself and other damage-responsive proteins, it appears that DNA-PK serves as both a sensor and a transducer of DNA-damage signals. The many roles of DNA-PK in the mammalian cell are discussed in this review with particular emphasis on recent advances in our understanding of the phosphorylation events that take place during the activation of DNA-PK at DNA breaks.
Burma
Sandeep
S
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. sburma@lbl.gov
Chen
David J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D016615:Telomere / Q000648:ultrastructure; D013912:Threonine / Q000737:chemistry; D045567:VDJ Recombinases / Q000378:metabolism
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C101467:XRCC4 protein, human; D013912:Threonine; D004247:DNA; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D045567:VDJ Recombinases