Numerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-strand breaks (DSBs), one of the most dangerous type of DNA damage along with interstrand crosslinks, are caused by ionizing radiation or certain chemicals such as bleomycin, and occur normally during the processes of DNA replication, meiotic exchange, and V(D)J recombination.
The two most prominent mechanisms for DSB repair are the error-free homologous recombination repair (HRR) pathway and the error-prone nonhomologous end-joining (NHEJ) pathway. The choice of the repair pathway may be determined by whether the DNA region has already replicated and the precise nature of the break. NHEJ functions at all stages of the cell cycle, but plays the predominant role in both the G1 phase and in S-phase regions of DNA that have not yet replicated (Rothkamm et al. 2003). HRR functions primarily in repairing both one-sided DSBs that arise at DNA replication forks and two-sided DSBs arising in S or G2-phase chromatid regions that have replicated. For a recent review, please refer to Ciccia and Elledge 2010.