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. Author manuscript; available in PMC: 2011 Oct 1.
Published in final edited form as: Semin Radiat Oncol. 2010 Oct;20(4):250–257. doi: 10.1016/j.semradonc.2010.05.002

Figure 1. Simplified schematic depicting steps in the non-homologous end-joining (NHEJ) pathway of DNA double-strand break (DSB) repair.

Figure 1

DSBs induced by ionizing radiation (IR) or chemotherapeutic agents are recognized by the Ku70/80 heterodimer which then recruits DNA-PKcs (DNA-dependent protein kinase, catalytic subunit) resulting in activation of the latter. Activated DNA-PKcs phosphorylates itself and other proteins involved in repair or damage signaling. Following DNA-end processing by nucleases (such as Artemis and WRN) and DNA polymerases (such as pol λ and pol μ), the ends are ligated together by a complex of XRCC4 (X-ray repair complementing defective repair in Chinese-hamster cells 4), DNA ligase IV, and XLF (XRCC4-like factor, also called Cernunnos). The exact choreography of events at a break and the precise nature of the protein sub-complexes that participate in the repair process may be flexible. As the kinase activity of DNA-PKcs is essential for NHEJ, small molecule inhibitors that bind to and block the kinase domain of DNA-PKcs are very potent radiosensitizers.