DNA Damage

Deoxyribonucleic acid (DNA) encodes the information necessary for all functions of life. Despite the critical importance of DNA, its chemical structure is susceptible to chemical and physical alterations including base damage and single- and double-strand break (DSB) induction. Cellular DNA damage results from both environmental exposures and endogenous sources from normal cellular metabolism. DNA damage in both the nuclear and mitochondrial genomes is associated with several human diseases including the development of cancer. The biological consequences of DNA damage are largely determined by a cell's DNA repair capabilities and the interaction of damaged DNA with the replication and transcription machinery. Technologies exist for the detection and measurement of cellular DNA damage in varying contexts. Key Concepts Estimated rates of induction of various deoxyribonucleic acid (DNA) lesions, including spontaneous hydrolysis and oxidative DNA damage, have been determined. Potential biological consequences of DNA damage include physiological conditions such as cancer, neurodegenerative diseases, heart disease and ageing. Various exogenous and endogenous sources induce DNA base lesions and strand breaks that can be detected by molecular and biochemical methods. Incorporation of damaged deoxyribonucleotides during DNA synthesis can occur due to errors committed by DNA polymerases and/or disruptions of nucleotide pool balance. Many of the features resulting from DNA packing into chromatin, including DNA–protein interactions and sequence context, greatly impact how damage is distributed within the genome. Mutational signatures of cancers arise from context-dependent DNA damage and can be attributed to specific types of DNA damage. DNA is often the target of chemotherapeutic drugs used to treat cancer, resulting in tumour cell death. Mitochondrial DNA damage can increase reactive oxygen species, leading to cell death and in certain instances give rise to mutations that contribute to cancer phenotypes.