Role of non-homologous end joining in the repair of DNA double-strand breaks

Of the various types of DNA damage that can occur within the mammalian cell nucleus, the DNA double-strand break (DSB) is perhaps the most dangerous. DSBs are induced by ionizing radiation, chemotherapeutic drugs, as well as by the byproducts of cellular metabolism. Understanding exactly how a mammalian cell responds to and repairs a DSB is very important because, on one hand, DSBs cause cancer while, on the other hand, DSBs are induced by chemotherapeutic agents to treat the disease. Of the two main mechanisms by which cells can repair DSBs, NHEJ (non-homologous end joining) and HR (homologous repair), NHEJ is the predominant repair pathway in mammalian cells. In this chapter we describe the main steps in the NHEJ pathway of repair highlighting major recent discoveries, and also provide a perspective on the link between defective NHEJ and human disease.