DNA-PKcs function regulated specifically by protein phosphatase 5.
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Wechsler T, Chen BP, Harper R, Morotomi-Yano K, Huang BC, Meek K, Cleaver JE, Chen DJ, Wabl M
DNA-PKcs function regulated specifically by protein phosphatase 5.
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1247-52. Epub 2004 Jan 20.
- PubMed ID
- 14734805 [ View in PubMed]
- 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.