DNA Damage

Bryn S Moore, Emory University School of Medicine, Atlanta, Georgia, USA
Lydia P Morris, Emory University School of Medicine, Atlanta, Georgia, USA
Paul W Doetsch, Emory University School of Medicine, Atlanta, Georgia, USA

Published online: September 2009

DOI: 10.1002/9780470015902.a0000557.pub2

Various biochemical and physical events alter the structure and properties of deoxyribonucleic acid (DNA), such as damage to the bases as well as single- and double-strand break (DSB) induction. The sources for cellular DNA damage include exposures to environmental chemicals and radiation as well as endogenous processes resulting from normal cellular metabolism. Conversion of DNA into these forms can have deleterious biological consequences for cells, including development of cancer and other detrimental outcomes. The basis for these biological endpoints is largely dependent on the interactions between the DNA damage and the cell's DNA replication and gene expression machinery. Technologies exist for the detection and measurement of DNA damage in cells. Each of these methods functions in different contexts and with varying degrees of sensitivity.

Key concepts

  • The rates of induction of various deoxyribonucleic acid (DNA) lesions, including spontaneous hydrolysis and oxidative DNA damage, have been estimated.
  • DNA damage has been associated with various physiological conditions including cancer, neurodegenerative diseases, heart disease and the process of ageing.
  • Damage from a variety of exogenous and endogenous sources induces DNA base lesions and strand breaks, which can be detected by various molecular and biochemical methods.
  • Damaged deoxyribonucleotides can be incorporated into DNA during synthesis due to errors by the polymerase and/or disruptions of nucleotide pool balance.
  • Many of the features of DNA in chromatin, including DNA–protein interactions and sequence context, greatly impact the manner in which damage is distributed within the genome.
  • Chemotherapeutic agents, used to treat cancers, often target DNA resulting in tumour cell death.

Keywords: DNA damage; DNA repair; mutation; cancer

Figure 1. Sites of chemical modification on DNA. The base (A, T, G, C), deoxyribose and phosphate building block components of DNA are vulnerable to attack by numerous exogenous and endogenous agents. Important examples of DNA modifications at various positions caused by spontaneous hydrolysis (open arrows), particularly at the N-glycosidic bond of G (I) to generate an abasic site or at the exocyclic amino group of U to form U (II). Other examples include radical attack by reactive oxygen species (ROS) at several positions (closed arrows) on the deoxyribose and bases such as C-8 of G to produce 8-oxoguanine (III). DNA contains many nucleophilic centres (stars) that are attractive sites for chemical reactions with exogenous and endogenous electrophilic chemicals such as alkylating agents. One example of an important mutagenic base modification is alkylation at the O6 position of G (IV).
Figure 2. Representative DNA-damage products. (a) The major endogenous DNA damages are depicted with alterations highlighted in red. Important examples shown here are, uracil (from cytosine deamination), cyclobutane pyrimidine dimer (produced by UV light exposure), 8-oxoguanine (produced by reactive oxygen species) and O6-methylguanine (produced by alkyating agents). Reproduced from Krwawicz et al., 2007. (b) DNA lesions including abasic site (primarily produced by spontaneous depurination and depyrimidination), pyrimidine dimers (generated by UV exposure) and cisplatin induced intra- and interstrand cross-links.
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Related Sub-Topics:

DNA Damage and Repair | Nucleic Acids: Structure, Function, Metabolism
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Article Title: DNA Damage
 
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Moore, Bryn S, Morris, Lydia P, and Doetsch, Paul W(Sep 2009) DNA Damage. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000557.pub2]