Cellular insults causing DNA damage can be of varied origins: endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiation and chemicals. Double strand breaks (DSBs), one of the most dangerous types of DNA damage, are caused by ionizing radiation or certain chemicals such as bleomycin, and also occur normally during the processes of DNA replication, meiotic exchange, and V(D)J recombination. Two distinct mechanisms for DSB repair are the error-free homologous recombination repair (HRR) pathway and the error-prone non-homologous end joining (NHEJ) pathway. The choice of 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 the G1 phase and in early S phase, when the lack of a duplicated sister chromosome prevents repair by HRR. In contrast, HRR functions primarily in repairing DSBs that occur either during the act of DNA replication, or DSBs that occur in late S or G2 phase in chromosomal regions that have already been replicated.