title: Involvement of DNA-dependent protein kinase in normal cell cycle progression through mitosis.
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.
authors.affiliation: Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: Kyung-Jong
authors.initials: KJ
authors.lastname: Lee
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Lin
authors.forename: Han-Yi
authors.initials: HY
authors.lastname: Chou
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Yajima
authors.forename: Kazi R
authors.initials: KR
authors.lastname: Fattah
authors.forename: Sheng-Chung
authors.initials: SC
authors.lastname: Lee
authors.forename: Benjamin P C
authors.initials: BP
authors.lastname: Chen
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology; D051747:DNA-Activated Protein Kinase / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects* / Q000235:genetics; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D051747:DNA-Activated Protein Kinase; D015739:Nocodazole