mutagenic DNA lesions
Damage to DNA can be classified as either cytotoxic or mutagenic.
Cytotoxic DNA lesions, including bulky lesions, interstrand crosslinks and double-strand breaks, interfere with transcription, replication or chromosome segregation.
Mutagenic DNA lesions, on the other hand, are defined as lesions that do not necessarily interfere with DNA metabolic processes, but if not removed before replication could cause miscoding resulting in mutations and subsequent carcinogenesis.
DNA-damage signalling mechanisms seem to have evolved primarily to respond to cytotoxic lesions, whereas DNA-repair mechanisms have evolved to deal with both classes of DNA lesions.
Bulky DNA lesions such as UV-light-induced pyrimidine dimers and cisplatin adducts, which cause great distortion in the DNA helix, can act as both cytotoxic and mutagenic lesions depending on their localization in the genome.
If they are located in the transcribed strand of active genes they are cytotoxic, as they can induce apoptosis by blocking transcription. lesions are suppressed by their removal through TCR, whereas similar lesions elsewhere in the genome are removed by another NER system, global genomic repair (GGR).
TCR is a specialized repair pathway using RNA polymerase II stalled at DNA lesions for recruitment of DNA-repair enzymes, whereas GGR requires sp
The cytotoxicities of theseecialized proteins for the detection of DNA lesions and recruitment of DNA-repair factors.
So, the function of TCR is primarily to counteract DNA-damage signalling and suppress apoptosis, whereas GGR removes pre-mutagenic lesions and thereby suppresses carcinogenesis. In fact, there is a strong correlation between the incident of lung and breast cancer and the capacity for NER of an individual.
See also
cytotoxic DNA lesions