Involvement of DNA-Dependent Protein Kinase in Normal Cell Cycle Progression through Mitosis
Resource
JOURNAL OF BIOLOGICAL CHEMISTRY v.286 n.14 pp.12796-12802
Journal
Journal of Biological Chemistry
Pages
12796-12802
Date Issued
2011
Date
2011
Author(s)
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.