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Abasic sites are potentially mutagenic and can be produced by spontaneous depurination and depyrimidination reactions.Depurination involves the loss of purine bases from DNA.Depyrimidination involves the loss of pyrimidine bases from DNA.Most types of deaminations produce a base that does not naturally occur in DNA, and this facilitates the identication and excision of the deaminated base by a DNA glycosylase enzyme.This event occurs at a rate of about bases per cell per day in mammalian cells, in spontaneous deamination reactions. Interestingly, one possible reason why the genetic code, which is thought to have been initially carried in RNA bases, was <a href="http://inhibit09.online/archives/192"></a> replaced by the current code carried in DNA bases is so a deaminated C converted to a U can be easily recognized as damage. The deamination of methylcytosine into thymine leads to the formation of a GT base pair, which is potentially mutagenic.However, some strand breaks are a serious form of DNA damage and inhibit DNA replication, leading to the activation of DNA repair mechanisms.DNA strand breaks can be caused by oxidative damage to DNA. Doublestrand breaks can also result from the blockage or pausing of DNA replication which can lead to replication fork collapse and free doublestranded ends. It is interesting to note that disruption of pathways involved in singlestrand break repair often results in neurological diseases rather than carcinogenesis or progeria.Because ROS are one of the major causes of singlestrand breaks, one possible explanation is that the oxygen consumption in the nervous system makes it more susceptible to defects in singlestrand break repair.Therefore, singlestrand breaks may contribute to neurological decline. Misrepaired doublestrand breaks lead to genomic rearrangements, a common and serious problem in ageing organisms. A   considerably increased frequency of DNA doublestrand breaks is observed in patients of some progeroid syndromes discussed earlier, such as WS and AT. The BER pathway can be categorized into two subpathways, namely shortpatch BER, where only one nucleotide is replaced; or longpatch BER, where nucleotides are replaced. The decision between performing a shortpatch or longpatch repair is modulated by PARP and PARP. One difference between these two subpathways is that in the longpatch pathway the WRN protein interacts physically and functionally with several other proteins such as PCNA and RPA, which is not the case in the shortpatch pathway, for at least two reasons.First, BER is the primary pathway to repair oxidative DNA damage, and this is the most likely kind of damage to occur in brain tissue, which is metabolically very active. Secondly, neurons are nondividing cells, and thus in principle other DNA repair pathways such as homologous recombination and mismatch repair are not important in neurons.There is good evidence that, overall, the level of BER activity is reduced with age.Out of those three pathways, BER seems the least associated with ageing, whilst the evidence for association with ageing is considerably stronger for the NER and NHEJ pathway.Note that this section does not cover some types of DNA repair that, although important, are not thought to be relevant for ageing.This kind of lesion interferes with base pairing and usually blocks transcription and normal replication.

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