1. Involvement of DNA-dependent protein kinase in normal cell cycle progression through mitosis
- Author
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Hirohiko Yajima, Kyung Jong Lee, Benjamin P C Chen, Yu Fen Lin, Kazi R. Fattah, Sheng-Chung Lee, and Han Yi Chou
- Subjects
Blotting, Western ,Immunoblotting ,Mitosis ,Polo-like kinase ,DNA-Activated Protein Kinase ,Biology ,DNA and Chromosomes ,Biochemistry ,PLK1 ,Microtubules ,Chromosome Segregation ,Humans ,Kinase activity ,Phosphorylation ,Molecular Biology ,Cells, Cultured ,Kinetochore ,Nocodazole ,Cell Cycle ,Cell Biology ,Cell cycle ,DNA repair protein XRCC4 ,Flow Cytometry ,HCT116 Cells ,Cell biology ,enzymes and coenzymes (carbohydrates) ,Centrosome ,biological phenomena, cell phenomena, and immunity ,HeLa Cells - 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 non-homologous 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.
- Published
- 2011