Types of DNA Lesions

P2 Most of the latter were associated with different types of DNA damage, indicating that DNA is one of the main targets for Cr inside the cell. The most prominent effect was on lacZ transcription from dinD promoter, which responded to all types of DNA lesion. RecA promoter... 

Vogel, E.W. (1989) Somatic cell mutagenesis in Drosophila, recovery of genetic damage in relation to the types of DNA lesions induced in mutationally unstable and stable X-chromo-somes. Mutat. Res.. 211. 153-170... 

Since the AKR pathway produces electrophilic and redox-active PAH o-quinones, two major types of DNA lesions are possible. These are the covalent adducts in which the PAH o-quinones are bound to bases in DNA and the oxidative lesions that can arise due to the production of ROS (Scheme 6.6). 

The exact nature of the lesion in DNA is unknown, and so is the type of DNA that is attacked. Recent X-ray crystallographic studies, as well as other physicochemical studies, have made it clear that DNA is not simply a polynucleotide, folded as Watson and Crick (106) proposed. There are three main conformational types of DNA they each keep the hydrogen-bonded bases in the center of the helix, but may tilt them by a "propellor twist," may slide them from the center of the helix in the plane of the base pairs, and may vary the amount of rotation from one base pair to the next up the helical axes. 

NER, a highly versatile pathway for DNA damage removal, is often dysfunctional in NSCLC and might therefore be the Achilles heel for customizing chemotherapy. NER removes numerous types of DNA helix-distorting lesions, including cisplatin- and ultraviolet-induced photo products (12). 

As mentioned above, one consequence of stalled RNA polymerase II at a DNA adduct is activation of transcription-coupled repair [27], This effect may depend on the type of polymerase, however, since the removal of some types of DNA damage is slower from RNA-polymerase I transcribed ribosomal DNA than from a nuclear gene [160], The lower level of repair in the nucleolus could also reflect the influence of other transcription factors, such as the HMG-domain protein UBF, which bind to cisplatin-mod-ified DNA [145]. When HeLa cells were exposed to cisplatin at concentrations which did not seem to affect nuclear transcription, inhibition of rDNA gene expression was associated with the redistribution of UBF, along with other factors responsible for rRNA transcription [138], These observations indicate how cisplatin might exert a combination of effects. Transcription is stopped due to titration of essential factors by the platinum-DNA adducts, and the same proteins could shield the lesions from the repair activity. 

There are two major types of DNA damage following UV radiation cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6-4) photoproducts that are often simply called (6-4) photoproducts. Formation of these UV lesions may be influenced by the DNA sequence. Nevertheless, in general, CPDs are more abundant than (6-4) photoproducts in UV irradiated DNA. For example, in UVC-irradiated DNA, the overall ratio of CPDs to (6-4) photoproducts is about 3 1. 

In contrast to the cell signal transduction mechanism, there are various types of DNA repair mechanisms [14, 15, 63] that are specialized in removing different kinds of DNA lesions. 

---