FIGURE 1 | Overview of DNA repair pathways involved in repairing toxic DNA lesions formed by cancer treatments.

The DNA-damaging agents that are used in cancer treatment induce a diverse spectrum of toxic DNA lesions. These lesions are recognized by a variety of DNA repair pathways which are lesion-specific but are complementary in some respects. a | Ionizing radiation and radiomimetic drugs induce double-strand breaks (DSBs) that are predominantly repaired by non-homologous end joining (NHEJ). b, c | Monofunctional alkylators (b) and bifunctional alkylators (c) induce DNA base modifications, which interfere with DNA synthesis. Lesions produced by some alkylators are processed into toxic lesions in a mismatch repair-dependent manner. The base-excision repair (BER) and nucleotide-excision repair (NER) pathways are, together with alkyltransferases (ATs), major repair pathways, whereas other repair pathways repair toxic replication lesions, such as those produced by interstrand crosslinks. d | Antimetabolites interfere with nucleotide metabolism and DNA synthesis, causing replication lesions which have not yet been characterized. Mismatch repair mediates the toxicity of some antimetabolites (for example, thiopurines). The repair pathways involved in repair of antimetabolite-induced lesions are, apart from BER, poorly characterized. e | Topoisomerase poisons trap topoisomerase I or II in transient cleavage complexes with DNA, thus creating DNA breaks and interfering with replication. f | Replication inhibitors induce replication fork stalling and collapse, resulting in indirect DSBs. The relative contributions of the major repair pathways to the respective types of DNA damage outlined are indicated by the sizes of the boxes. This is based on the extent of sensitivity of repair-deficient cells to anticancer drugs in each category. ENDO, endonuclease-mediated repair; FA, Fanconi anaemia repair pathway; HR, homologous recombination; O₂G, DNA dioxygenases; RecQ, RecQ-mediated repair; SSBR, DNA single-strand break repair; TLS, translesion synthesis.

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