DNA-PKcs function regulated specifically by protein phosphatase 5

Thomas Wechsler, Benjamin P C Chen, Ryan Harper, Keiko Morotomi-Yano, Betty C B Huang, Katheryn Meek, James E. Cleaver, David J. Chen, Matthias Wabl

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1247-1252
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
StatePublished - Feb 3 2004

ASJC Scopus subject areas

  • General


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