Strategies for the evaluation of DNA damage and repair mechanisms in cancer

Abstract

DNA lesions and the repair mechanisms that maintain the integrity of genomic DNA are important in preventing carcinogenesis and its progression. Notably, mutations in DNA repair mechanisms are associated with cancer predisposition syndromes. Additionally, these mechanisms maintain the genomic integrity of cancer cells. The majority of therapies established to treat cancer are genotoxic agents that induce DNA damage, promoting cancer cells to undergo apoptotic death. Effective methods currently exist to evaluate the diverse effects of genotoxic agents and the underlying molecular mechanisms that repair DNA lesions. The current study provides an overview of a number of methods that are available for the detection, analysis and quantification of underlying DNA repair mechanisms.

Keywords: DNA damage; DNA repair; double-strand break; single-strand break.

Figure 1.

Summary of distinct types of DNA lesions, the repair pathways involved in their repair and the experimental strategies that are used to evaluate each type. ROS, reactive oxygen species; UV, ultraviolet; BER, base excision repair; NER, nucleotide excision repair; DDR, DNA damage repair; MMR, mismatch repair; NHEJ, non-homologous end joining; HR, homologous recombination; SSR, single strand repair; TLS, translesion synthesis; BIR, base incision repair; COMET, single-cell gel electrophoresis; TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labeling; HPLC-MS, high performance liquid chromatography-mass spectrometry; DBD-FISH, DNA breakage detection-fluorescence in situ hybridization; GC-MS, gas chromatography-mass spectrometry; XRCC1, X-ray repair cross complementing 1; EM, electrochemical methods; IHC, immunohistochemistry; TDPCR, terminal transferase-dependent polymerase chain reaction; LMPCR, ligation-mediated polymerase chain reaction; ICPCR, immune-coupled polymerase chain reaction; RIA, radioimmunoassay; ELISA, enzyme-linked immunosorbent assay; LAM-HTGTS, linear amplification-mediated high-throughout genome-wide translocation sequencing; PCR, polymerase chain reaction.