Neurodegenerative disease and the repair of oxidatively damaged DNA Book Chapter

Cooke, MS. (2005). Neurodegenerative disease and the repair of oxidatively damaged DNA . 131-140. 10.1017/CBO9780511544873.011



cited authors

  • Cooke, MS

fiu authors

abstract

  • Free radicals and oxidative damage to DNA In addition to endogenous sources of free radicals, such as those derived from normal metabolism (see Chapter 1), pathophysiological or environmental events may also generate free radicals. Cellular biomolecules, including nucleic acids, proteins and lipids are all targets for these damaging species. Reactive oxygen species (ROS) are of particular interest. Enzymic and non-enzymic antioxidants (discussed in Chapter 2) contribute to the limit on the extent to which ROS are produced, and hence their interaction with cellular components. If the balance between the anti- and pro-oxidant factors is altered in favour of the latter, a condition of oxidative stress arises, with a concomitant increase in biomolecule modification. Given its central role in cellular events, modification of DNA, for example 8-hydroxyguanine (8-OH-Gua), and thymine glycol (Tg), has been the subject of intense study. Such lesions may have a plethora of effects, most notably mutation, but also replicative block, deletions, microsatellite instability and loss of heterozygosity, as well as various epigenetic effects (for review see Cooke et al., 2003). Furthermore, a great deal of literature exists that describes elevated levels of lesions in a variety of diseases, suggesting that the induction of damage is an important event in pathogenesis (for review, see Cooke et al., 2003). Unlike oxidatively modified lipids and proteins, which may be removed and replaced as part of normal turnover, DNA needs to be repaired, and intense study has revealed much about the processes that maintain genome integrity.

publication date

  • January 1, 2005

Digital Object Identifier (DOI)

start page

  • 131

end page

  • 140