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Oxidative DNA Damage; Mechanisms of Product Formation and Repair By Base-Excision Pathway

Published

Author(s)

M Miral Dizdar

Abstract

Free radicals such as OH, eaq- and H atoms react with DNA by addition to bases or abstraction of H atoms from the sugar moiety. Oxygen adds to base or sugar radicals of DNA resulting in formation of peroxyl radicals. DNA radicals further react to give multiple final products from each of the DNA bases and the sugar moiety by a variety of mechanisms. Types of products and their yields depend on the type of free radicals and reaction conditions. DNA-protein crosslinks are formed by reactions of DNA radicals with proteins or protein radicals. DNA base and sugar products and DNA-protein crosslinks can be measured by a variety of analytical techniques. Different results may be obtained by different techniques and methodologies. Many of these products were identified in living cells exposed to free radical generating systems. DNA products are repaired by several repair pathways. Base products are mainly repaired by base-excision pathway. DNA glycosylases are involved in the first step of this type of repair and remove modified bases from DNA. Some enzymes are specific for pyrimidine-derived lesions whereas others remove purine-derived lesions. There are also repair enzymes with cross reactivity excising both pyrimidine- and purine-derived lesions. Excision kinetics depends on the enzyme and DNA substrates. Single mutations in DNA repair enzymes significantly alter the specificities of DNA glycosylases. DNA base products are repaired in cells by varying kinetics. Purine-derived lesions possess longer half-lives of excision than pyrimidine-derived lesions. A number of products were investigated for their biological effects. The biological consequences of free radical-damaged DNA in cells are largely unknown and await further exploration.
Citation
Free Radicals in Chemistry, Biology and Medicine
Volume
7
Publisher Info
OICA International, London,

Keywords

DNA glycosylases, DNA repair, mutagenesis, Oggl proteins, oxidative DNA damage, single mutations

Citation

, M. (2000), Oxidative DNA Damage; Mechanisms of Product Formation and Repair By Base-Excision Pathway, Free Radicals in Chemistry, Biology and Medicine, OICA International, London, (Accessed April 23, 2024)
Created May 1, 2000, Updated February 19, 2017