Endogenous Repair System of Oxidative Damage of DNA

Abstract

DNA is one of the most important biomolecules of living cells which carries genetic information from generation to generation. Many endogenous and exogenous agents may disrupt the structure of DNA. Change in the cellular genome can lead to errors in replication, transcription and in protein synthesis. DNA damage occurs naturally or result from a metabolic and hydrolytic process which release some very active chemical entities like free radicals, Reactive Oxygen Species (ROS), Reactive Nitrogen Intermediate (RNI), Reactive Carbonyl Species (RCS), lipid peroxidation products and alkylating agents. Superoxide radical, hydroxyl radical and hydrogen peroxide cause a significant threat to cellular integrity by damaging the DNA, lipids, proteins and other biomolecules. Oxidative stress may be explained as a disturbance in the number of free radicals and our system’s ability to neutralize these free radicals. Imbalances in the normal redox potential can also lead to toxic effects via the generation of peroxides. Oxidation of DNA bases leads to the base damage, nick in the strand and break in the strand either single or double strand. Oxidative stress can also cause modifications in normal mechanisms of cell signaling. DNA mutation can result in a number of genetic abnormalities such as cancer, heart failure, Alzheimer’s disease, and depression. Human body has special protection in the form of antioxidant molecules and enzymes against these free radicals. Generation of ROS and its neutralization must be regulated to protect cells and signalling biomolecules from the deleterious effect of oxidative stress with the involvement of antioxidant systems, enzymes, and specific proteins. DNA repair system is a complex system which helps in the identification, removal of the wrong nucleotide and repairs them and as a result, the cell will produce correct and functional protein and active enzyme.