Types and consequences of DNA damage

See also Pyrimidine Dimers, O -Alkylguanine Alkytransferase, Types and Consequences of DNA Damage, Light Absorbing Pigments (from Chapter 17), Photochemistry (from Chapter 17), Photosystem Summary (from Chapter 17)... 

See also Photo reactivation. Types and Consequences of DNA Damage, Thymine Dimers... 

There are three main types of DNA damage that can be repaired by cellular processes missing, incorrect, or altered bases interstrand cross-links and strand breaks. These types of DNA damage can be induced by some chemicals, and there is increasing evidence that these chemicals are carcinogenic. Therefore, procedures that can detect damage to DNA or its consequences are potentially valuable to predict carcinogenic activity.1 1... 

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. 

The interrelationships described above provide a basis for evaluating the possibility that chemotherapeutic or metabolic manipulation can be used to produce drastic alterations in ceU functions. We have shown that one mechanism of cell death, which we have called Type 1 or the Suicide mechanism, is mediated by activation of poly(ADP-ribose) polymerase and the consequent depletion of cellular energy metabolites (1,2). This enzyme is activated by DNA strand breaks to cleave NAD at the glycosylic bond between the nicotinamide and adenosine diphosphoribose moieties (3). The latter are joined by the same enzyme into linear or branched chain polymers of ADP-ribose (3). Poly(ADP-ribose) polymerase activity and utilization of its substrate, NAD, are proportional to the number and duration of DNA strand breaks (4, 5). As shown in Fig. 2, DNA damage can sufficiently... 

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