Introduction To Serial Reviews On Oxidative DNA Damage And Repair
Free radicals are produced in cells by cellular metabolism and by exogenous sources such as carcinogenic compounds, redox-cycling drugs and ionizing radiations. Reactive species cause damage to cells by reacting with molecules such as DNA, proteins and lipids. DNA damage caused by oxygen-derived species including free radicals is the most frequent type encountered by aerobic cells. When this type of damage occurs to DNA, it is called oxidative DNA damage and it can produce a multiplicity of modifications in DNA including base and sugar lesions, strand breaks, DNA-protein crosslinks and base-free sites. Many such lesions have been identified in cells and tissues at steady-state levels and upon exposure to free radical-generating systems. Data accumulated over many years clearly show that oxidative DNA damage plays an important role in a number of disease processes. Thus, oxidative DNA damage is implicated in carcinogenesis and neurodegenerative diseases such as Alzheimer's disease. There is also strong evidence for the role of this type of DNA damage in the aging process. The accumulation of oxidative DNA damage in non-dividing cells is thought to contribute to age-associated diseases. DNA damage is countered in cells by DNA repair, which is a basic and universal process to protect the genetic integrity of organisms. The genomes of organisms encode DNA repair enzymes that continuously monitor chromosomes to correct DNA damage. Multiple processes such as base- and nucleotide-excision pathways exist to repair the wide range of DNA damage. If left unrepaired, oxidative DNA damage can lead to detrimental biological consequences in organisms, including cell death, mutations and transformation of cells to malignant cells. Therefore, DNA repair is regarded as one of the essential events in all life forms. There is an increasing awareness of the importance of oxidative DNA damage and its repair to human health. Thus, it becomes exceedingly important to understand, at the fundamental level, the mechanisms of oxidative DNA damage, and its processing by DNA repair enzymes as well as how unrepaired DNA lesions may lead to cytotoxicity, mutagenesis and eventually to diseases and aging. More detailed knowledge of mechanisms of DNA damage and repair might allow us to modulate DNA repair. This could lead to drug developments and clinical applications including the improvement of cancer therapy by inhibiting DNA repair in drug- or radiation-resistant tumors and/or the increase in the resistance of normal cells to DNA damage by overexpressing DNA repair genes.This series of Serial Reviews in FRBM deals with oxidative damage to DNA and its repair. It encompasses the contributions of the leading experts, who have performed research for many years in this field of science. The articles review mechanistic aspects of oxidative DNA damage, product formation, measurement of products, various pathways of DNA repair, damage recognition and removal of damaged sites in DNA by repair enzymes, and biological consequences of DNA lesions. It is hoped that this part of the FRBM Serial Reviews will be helpful to scientists, who work in the field of oxidative DNA damage and repair, and to those who would like to be involved in this important field of science.