Types of DNA Damage

Since the sources of DNA damage can be roughly divided into two main groups, endogenous damage and exogenous damage. The endogenous damages are the damage caused by reactive oxygen species or some agents else produced from normal metabolic byproducts, while exogenous damages are caused by external agents, like some radiations, include UV, x-rays; plant toxins; chemicals; viruses[1] and so on.

According different damage sources, there're different types of DNA damages.

Figure. 1 Genomic DNA is continually being damaged. This shows the possible types of damage that can occur

There are five main types of damage to DNA due to endogenous cellular processes:

        1. Oxidation of bases [e.g. 8-oxo-7,8-dihydroguanine (8-oxoG)] and generation of DNA strand interruptions from reactive oxygen species. 

        2. Alkylation of bases (usually methylation), such as formation of 7-methylguanine, 1-methyladenine, 6-O-Methylguanine.

        3. Hydrolysis of bases, such as deamination, depurination, and depyrimidination. 

        4. "Bulky Adduct Formation" (i.e., benzo[a]pyrene diol epoxide-dG adduct, aristolactam I-dA adduct) 

        5. Mismatch of bases, due to errors in DNA replication, in which the wrong DNA base is stitched into place in a newly forming DNA strand, or a DNA base is skipped over or mistakenly inserted.

Damage caused by different exogenous agents result in different damages. Some examples are:

        1. UV-B light causes crosslinking between adjacent cytosine and thymine bases creating pyrimidine dimers. This is called direct DNA damage.

        2. UV-A light creates mostly free radicals. The damage caused by free radicals is called indirect DNA damage.

        3. Ionizing radiation such as that created by radioactive decay or in cosmic rays causes breaks in DNA strands. Low-level ionizing radiation may induce irreparable DNA damage (leading to replicational and transcriptional errors needed for neoplasia or may trigger viral interactions) leading to pre-mature aging and cancer.[2][3][4]
        
        4. Thermal disruption at elevated temperature increases the rate of depurination (loss of purine bases from the DNA backbone) and single-strand breaks. For example, hydrolytic depurination is seen in the thermophilic bacteria, which grow in hot springs at 40-80 °C.[5][6] The rate of depurination (300 purine residues per genome per generation) is too high in these species to be repaired by normal repair machinery, hence a possibility of an adaptive response cannot be ruled out.

        5. Industrial chemicals such as vinyl chloride and hydrogen peroxide, and environmental chemicals such as polycyclic aromatic hydrocarbons found in smoke, soot and tar create a huge diversity of DNA adducts- ethenobases, oxidized bases, alkylated phosphotriesters and Crosslinking of DNA just to name a few.

UV damage, alkylation/methylation, X-ray damage and oxidative damage are examples of induced damage. Spontaneous damage can include the loss of a base, deamination, sugar ring puckering and tautomeric shift.[7]

1. Roulston A, Marcellus RC, Branton PE (1999). Viruses and apoptosis, Annu. Rev. Microbiol. 53: 577-628.
2. Acharya, PVN; The Effect of Ionizing Radiation on the Formation of Age-Correlated Oligo Deoxyribo Nucleo                     Phospheryl Peptides in Mammalian Cells; 10th International Congress of Gerontology, Jerusalem. Abstract No. 1; January 1975. Work done while employed by Dept. of Pathology, University of Wisconsin, Madison.
3. Acharya, PVN; Implicatons of The Action of Low-Level Ionizing Radiation on the Inducement of Irreparable DNA Damage Leading to Mammalian Aging and Chemical Carcinogenesis.; 10th International Congress of Biochemistry, Hamburg, Germany. Abstract No. 01-1-079; July 1976. Work done while employed by Dept. of Pathology, University of Wisconsin, Madison.
4. Acharya, PV Narasimh; Irreparable DNA-Damage by Industrial Pollutants in Pre-mature Aging, Chemical Carcinogenesis and Cardiac Hypertrophy: Experiments and Theory; 1st International Meeting of Heads of Clinical Biochemistry Laboratories, Jerusalem, Israel. April 1977. Work conducted at Industrial Safety Institute and Behavioral Cybernetics Laboratory, University of Wisconsin, Madison.
5. Madigan MT, Martino JM (2006). Brock Biology of Microorganisms (11th ed.). Pearson. p. 136.
6. Ohta, Toshihiro; Shin-ichi, Tokishita; Mochizuki, Kayo; Kawase, Jun; Sakahira, Masahide; Yamagata, Hideo (2006). "UV Sensitivity and Mutagenesis of the Extremely Thermophilic Eubacterium Thermus thermophilus HB27" Genes and Environment 28 (2): 56–61.
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