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Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1247-52. Epub 2004 Jan 20.

DNA-PKcs function regulated specifically by protein phosphatase 5.

Author information

1
Department of Microbiology and Immunology and UCSF Cancer Center, University of California, San Francisco, CA 94143, USA.

Abstract

Unrepaired DNA double-strand breaks can lead to apoptosis or tumorigenesis. In mammals double-strand breaks are repaired mainly by nonhomologous end-joining mediated by the DNA-PK complex. The core protein of this complex, DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself. Although the (auto)phosphorylation activity has been shown to be essential for repair of both random double-strand breaks and induced breaks at the immunoglobulin locus, the corresponding phosphatase has been elusive. In fact, to date, none of the putative phosphatases in DNA double-strand break repair has been identified. Here we show that protein phosphatase 5 interacts with DNA-PKcs and dephosphorylates with surprising specificity at least two functional sites. Cells with either hypo- or hyperphosphorylation of DNA-PKcs at these sites show increased radiation sensitivity.

PMID:
14734805
PMCID:
PMC337038
DOI:
10.1073/pnas.0307765100
[Indexed for MEDLINE]
Free PMC Article

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