TY - JOUR
T1 - Protein kinase CK2 localizes to sites of DNA double-strand break regulating the cellular response to DNA damage
AU - Olsen, Birgitte B.
AU - Wang, Shih Ya
AU - Svenstrup, Tina H.
AU - Chen, Benjamin P C
AU - Guerra, Barbara
N1 - Funding Information:
We thank Christian Rønn Hansen (Odense University Hospital) for technical assistance with the cell irradiation experiments. This work was supported by grants from the Danish Cancer Society (DP08152) and the Danish Natural Science Research Council (272-07-0258) to BG.
PY - 2012/3/9
Y1 - 2012/3/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84857938688&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857938688&partnerID=8YFLogxK
U2 - 10.1186/1471-2199-13-7
DO - 10.1186/1471-2199-13-7
M3 - Article
C2 - 22404984
AN - SCOPUS:84857938688
SN - 1471-2199
VL - 13
JO - BMC Molecular Biology
JF - BMC Molecular Biology
M1 - 7
ER -