Double-Strand Break Recognition and Its Repair by Nonhomologous End Joining

Abstract:: Many different agents can damage DNA, often with disastrous consequences. The most dangerous form of DNA damage is the double-strand break (DSB)—a single unrepaired DSB can induce a cell to undergo apoptosis. DSBs can also directly inactivate key genes, lead to chromosomal translocations, or generate unstable chromosomal abnormalities, which may ultimately lead to cancer development. DSBs are induced by ionizing radiation and radiomimetic chemicals but can also be generated during site-specific recombination events (for example, during V(D)J recombination in the immune system and meiotic recombination) and during DNA replication. Because the effects of DNA DSBs are potentially so serious, eukaryotes have elaborate systems to repair the damagerapidly or to stop DNA replication and cell division until the damage has been repaired. This chapter considers nonhomologous end joining (NHEJ), a major DSB repair system, drawing on data obtained from the mammalian system and the highly conserved Saccharomyces cerevisiae system.

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