Protein kinase CK2 localizes to sites of DNA double-strand break regulating the cellular response to DNA damage

Birgitte B. Olsen, Shih Ya Wang, Tina H. Svenstrup, Benjamin P C Chen, Barbara Guerra

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background: The DNA-dependent protein kinase (DNA-PK) is a nuclear complex composed of a large catalytic subunit (DNA-PKcs) and a heterodimeric DNA-targeting subunit Ku. DNA-PK is a major component of the non-homologous end-joining (NHEJ) repair mechanism, which is activated in the presence of DNA double-strand breaks induced by ionizing radiation, reactive oxygen species and radiomimetic drugs. We have recently reported that down-regulation of protein kinase CK2 by siRNA interference results in enhanced cell death specifically in DNA-PKcs-proficient human glioblastoma cells, and this event is accompanied by decreased autophosphorylation of DNA-PKcs at S2056 and delayed repair of DNA double-strand breaks.Results: In the present study, we show that CK2 co-localizes with phosphorylated histone H2AX to sites of DNA damage and while CK2 gene knockdown is associated with delayed DNA damage repair, its overexpression accelerates this process. We report for the first time evidence that lack of CK2 destabilizes the interaction of DNA-PKcs with DNA and with Ku80 at sites of genetic lesions. Furthermore, we show that CK2 regulates the phosphorylation levels of DNA-PKcs only in response to direct induction of DNA double-strand breaks.Conclusions: Taken together, these results strongly indicate that CK2 plays a prominent role in NHEJ by facilitating and/or stabilizing the binding of DNA-PKcs and, possibly other repair proteins, to the DNA ends contributing to efficient DNA damage repair in mammalian cells.

Original languageEnglish (US)
Article number7
JournalBMC Molecular Biology
Volume13
DOIs
StatePublished - Mar 9 2012

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Casein Kinase II
Double-Stranded DNA Breaks
DNA Damage
DNA
DNA-Activated Protein Kinase
DNA Repair
Catalytic DNA
Gene Knockdown Techniques
Glioblastoma
Ionizing Radiation
Histones
Small Interfering RNA
Reactive Oxygen Species
Catalytic Domain
Cell Death
Down-Regulation
Phosphorylation

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Protein kinase CK2 localizes to sites of DNA double-strand break regulating the cellular response to DNA damage. / Olsen, Birgitte B.; Wang, Shih Ya; Svenstrup, Tina H.; Chen, Benjamin P C; Guerra, Barbara.

In: BMC Molecular Biology, Vol. 13, 7, 09.03.2012.

Research output: Contribution to journalArticle

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