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Open Access Highly Accessed Research article

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

Birgitte B Olsen1, Shih-Ya Wang2, Tina H Svenstrup1, Benjamin PC Chen2 and Barbara Guerra1*

Author Affiliations

1 Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark

2 Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA

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BMC Molecular Biology 2012, 13:7  doi:10.1186/1471-2199-13-7

Published: 9 March 2012

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.