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

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.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.A wide variety of lesion types can affect the DNA requiring the intervention of distinct and lesion-specific DNA-repair mechanisms. However, it is known that repair mechanisms may complement each other in some respects by sharing many protein components [1]. DNA double-strand breaks (DSBs) induced, for instance, by ionizing radiation (IR) and radiomimetic drugs are difficult to repair and extremely toxic although they do not occur as frequently as other types of DNA lesion [1,2]. DSBs are repaired by two main mechanisms: non-homologous end-joining (NHEJ) and homologous recombination (HR). NHEJ is the major repair mechanism in mammalian cells whereas HR is the predominant repair mechanism in budding yeast [2]. In NHEJ, DNA lesions are recognized by the Ku70/80 heterodimer. Localization of Ku to sites of DSB serves to recruit other NHEJ proteins such as the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), ligases and polymerases [3,4]. The convergence of so many proteins to sites of DNA lesion is thought to protect at first the DNA ends from nucleases attack and later to facilitate the repair process. DNA-PKcs is a Ser/Thr kinase characterized by a weak activity that is significantly