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 journalArticle

103 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1247-1252
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number5
DOIs
StatePublished - Feb 3 2004

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Double-Stranded DNA Breaks
Phosphoric Monoester Hydrolases
DNA
DNA End-Joining Repair
DNA-Activated Protein Kinase
Radiation Tolerance
Immunoglobulins
Mammals
Carcinogenesis
Phosphorylation
Apoptosis
protein phosphatase 5
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

DNA-PKcs function regulated specifically by protein phosphatase 5. / Wechsler, Thomas; Chen, Benjamin P C; Harper, Ryan; Morotomi-Yano, Keiko; Huang, Betty C B; Meek, Katheryn; Cleaver, James E.; Chen, David J.; Wabl, Matthias.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 5, 03.02.2004, p. 1247-1252.

Research output: Contribution to journalArticle

Wechsler, T, Chen, BPC, Harper, R, Morotomi-Yano, K, Huang, BCB, Meek, K, Cleaver, JE, Chen, DJ & Wabl, M 2004, 'DNA-PKcs function regulated specifically by protein phosphatase 5', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 5, pp. 1247-1252. https://doi.org/10.1073/pnas.0307765100
Wechsler, Thomas ; Chen, Benjamin P C ; Harper, Ryan ; Morotomi-Yano, Keiko ; Huang, Betty C B ; Meek, Katheryn ; Cleaver, James E. ; Chen, David J. ; Wabl, Matthias. / DNA-PKcs function regulated specifically by protein phosphatase 5. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 5. pp. 1247-1252.
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