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DNA Repair (Amst). 2004 Aug-Sep;3(8-9):909-18.

Role of DNA-PK in the cellular response to DNA double-strand breaks.

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  • 1Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. sburma@lbl.gov

Abstract

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.

PMID:
15279776
[PubMed - indexed for MEDLINE]
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