Table 1.
Endogenous and exogenous sources of DNA damage, types of DNA lesions produced, repair mechanisms activated, and consequences on the DNA structure and processes
| Damaging event | Major forms of lesion | Repair mechanisms | Consequences on DNA | |
|---|---|---|---|---|
| Endogenous factors | Oxidation (ROS) | Oxidative base modifications | Base excision repair | Serve as miscoding template causing mutagenesis; helix distortion |
| SSBs | Single strand break repair or double strand break repair pathways | Collapse of DNA and RNA polymerase complexes; recombination events | ||
| Alkylation (SAM) | Methylated bases | Direct reversal; base excision repair; mismatch repair | G→A and T→C mutations; Inhibition of DNA replication | |
| Hydrolysis | AP sites | Base excision repair; lesion bypass | Misincorporation of bases; DNA or RNA polymerase block | |
| Deaminated bases (uracil) | DNA glycosylase & base excision repair | Changes in coding properties causing mutagenesis | ||
| Polymerase incorporation errors | Base substitutions, insertions or deletions | Mismatch repair | Mutagenic outcomes and genomic instability; fork collapse | |
| Exogenous factors | Ionizing radiation | DSBs | Non-homologous end-joining; Homologous recombination | Mutagenesis, chromosomal translocation and rearrangements; genomic instability |
| SSBs | AP endonucleases | Polymerase block | ||
| Single base alterations (mostly oxidation) | Base excision repair | |||
| Ultraviolet radiation | CPDs and 6-4PPs | Nucleotide excision repair | Mutagenicity (C to T and T to C transversions and CC to TT transition mutations); helix distortion; error-prone bypass | |
| Chemical agents (aromatic amines, alkylating agents, PAHs, reactive electrophiles, natural toxins, chemotherapeutic agents) | Base lesions and DNA adducts | Nucleotide excision repair; direct reversal; base excision repair; mismatch repair | Base substitutions; frameshift mutations; replication and transcription block; destabilization and breakage of DNA; helix distortion | |
| Intrastrand or interstrand crosslinks | Nucleotide excision repair; homologous recombination | Structure disruption; inhibition of DNA replication and transcription |