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For a long time the brain was a neglected organ in terms of studies on DNA tran sactions.Such neglect was not because the brain was consider ed unimpor tant, butprimarilybecause the postmitotic nature of adult brain cells results in low levels of DNA synthesis and repair.Over the past two decades, however, our everincreasing knowledge of neurological disorders and the striking susceptibility of the brain to oxidative DNA damage have resulted in considerable attention being focused on improving our understanding of the brains DNA repair pathways and genomic stability.The purpose of this article is to review the current state of knowledge regarding neurological diseases that have been found to be linked to a mutation in a crucial component of a DNA repair pathway.It will focus on the relationship between a given neurological disorder and the type of DNA repair pathway that is compromised, with special emphasis given to oxidative DNA damage and its repair.DNA DAMAGE IN MAMMALIAN CELLS DNA, being a chemical consisting of base, deoxyribose and phosphate moieties, is vulnerable to attack by other chemicals, which can result in alterations to its coding properties.Damage to the native structure of DNA can occur through two main mechanisms: spontaneous damage <a href="http://www.targetmol.com/compound/Histamine">Targetmol's Histamine</a> caused by sources within a cells metabolism, and damage caused by external sources such as chemicals and radiation.Protracted oxidative, hydrolytic, deamina tion or alkylation reactions within a cell can modify DNA bases, or even sometimes cause a complete loss of bases within DNA, resulting in strand breakage.The neuronal cellular machinery is endowed with various DNA repair pathways to counteract such damaging events.The past years have seen a great advancement in our understanding of the various DNA repair pathways, both in prokaryotes and in higher organisms.Bacterial photolysis activity is an example of direct reversal of DNA damage.In this repair system an enzyme, with the help of light, monomerizes the pyrimidine dimers in DNA.It is not clear, however, whether a comparable process occurs in humans, so this mode of repair will not be discussed further here.This pathway is responsible for repairing a wide variety of DNA lesions, ranging from simple base methylations, to interstrand adduct formation that results in major distortion of the DNA structure.The basic process involved in this pathway consists of four steps: first, recognition and demarcation of the damaged site; second, excision of the damaged portion of DNA and certain adjacent sequences; third, resynthesis of the excised portion using the second strand as a template; and last, ligation of the newly synthesized portion to the existing downstream sequence.As knowledge of the excision repair pathway increased, it became clear that it can be viewed as two distinct streamsNER and BER.Nucleotide excision repair NER is a multistep process that seems to come into operation to repair such DNA damage as the distinct helical distortion caused by ultravioletinduced photoproducts.The first step involves damage recognition and demarcation, and requires, possibly among many other   factors, three proteinsthe xeroderma pigmentosum comp lement ing proteins DDB and XPC, and RDB centrin. The second step involves the simultaneous arrival of the DNA excision repair proteins ERCC and ERCC, resulting in a dual incision on either side of the damage and removal of an oligonucleotide consisting of around nucleotides.

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