DNADamage

Abstract

Deoxyribonucleic acid (DNA) is composed of bases that code for all functions of life. Biochemical and physical events that alter DNA include base damage and single‐ and double‐strand break (DSB) induction. Cellular DNA damage is induced through exposure to environmental chemicals and radiation, as well as from endogenous sources including normal cellular metabolism. Notably, DNA damage can occur in both the nuclear and mitochondrial genomes. Damaged DNA can lead to deleterious biological outcomes including cancer development and other diseases. Whether biological consequences arise from DNA damage largely depends on the DNA repair capacity of the cell and the interactions of the DNA damage and DNA replication machinery. Detection and measurement of cellular DNA damage is accomplished through methods that vary in sensitivity and DNA damage context. Key Concepts: Estimated rates of induction of various deoxyribonucleic acid (DNA) lesions, including spontaneous hydrolysis and oxidative DNA damage, have been determined. Potential biological outcomes 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 various molecular and biochemical methods. Incorporation of damaged deoxyribonucleotides during DNA synthesis can occur owing 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 affect the manner in which damage is distributed within the genome. Cancer mutational signatures arise from context‐dependent DNA damage, and certain signatures 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.