Involvement of DNA-dependent protein kinase in normal cell cycle progression through mitosis

Kyung Jong Lee, Yu Fen Lin, Han Yi Chou, Hirohiko Yajima, Kazi R. Fattah, Sheng Chung Lee, Benjamin P C Chen

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) plays an important role in DNA double-strand break (DSB) repair as the underlying mechanism of the nonhomologous end joining pathway. When DSBs occur, DNA-PKcs is rapidly phosphorylated at both the Thr-2609 and Ser-2056 residues, and such phosphorylations are critical for DSB repair. In this study we report that, in addition to responding to DSBs, DNA-PKcs is activated and phosphorylated in normal cell cycle progression through mitosis. Mitotic induction of DNA-PKcs phosphorylation is closely associated with the spindle apparatus at centrosomes and kinetochores. Furthermore, depletion of DNA-PKcs protein levels or inhibition of DNA-PKcs kinase activity results in the delay of mitotic transition because of chromosome misalignment. These results demonstrate for the first time that DNA-PKcs, in addition to its role in DSB repair, is a critical regulator of mitosis and could modulate microtubule dynamics in chromosome segregation.

Original languageEnglish (US)
Pages (from-to)12796-12802
Number of pages7
JournalJournal of Biological Chemistry
Volume286
Issue number14
DOIs
StatePublished - Apr 8 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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