Sources of DNA damage and their repair. Endogenous and environmental sources of DNA damage are shown in green boxes, with the lesions they cause in beige boxes (where known, the approximate number of the indicated type of lesion that occurs naturally in a cell each day is shown). Therapeutic DNA-damaging agents that cause the corresponding DNA lesion are shown in orange boxes. DNA repair pathways (blue boxes) repair DNA damage that is induced by endogenous and environmental DNA-damaging agents and thus protect the genome but they antagonize the efficacy of therapeutic DNA-damaging agents (except for mismatch repair (MMR)). BER, base excision repair; HRR, homologous recombination repair; ICL, interstrand crosslink; IR, ionizing radiation; MMC, mitomycin C; NER, nucleotide excision repair; NHEJ, non-homologous end joining; ROS, reactive oxygen species; SAM, S‑adenosyl methionine; SSB, single-strand break; SSBR, SSB repair; TMZ, temozolomide; TOPO, topoisomerase; UV, ultraviolet