When does DNA damage occur?

DNA damage can be caused by endogenous processes and exogenous sources. Exogenous sources of damage include UV radiation, ionizing radiation, and different chemical substances. Ionizing radiation includes high-energy particles or electromagnetic waves that have enough energy to ionize atoms and molecules. Exposure to ionizing radiation is associated with an increased risk of DNA double-strand breaks. Some examples include X-rays, gamma rays, and cosmic radiation. UV radiation comes from the sun and other sources like tanning beds. When UV radiation directly interacts with DNA, it primarily causes the formation of pyrimidine dimers. UV-induced DNA damage can cause mutations, particularly in genes involved in skin cancer. Polycyclic aromatic hydrocarbons (PAHs), and aromatic amines are examples of chemicals that can damage DNA.

Endogenous processes that cause DNA damage include alkylation, oxidation, hydrolysis, and mismatch of DNA bases. Mismatched DNA bases can lead to errors in the DNA sequence. The failure to repair mismatched bases can result in mutations. Alkylating substances can cause incorrect pairing of nucleotides in DNA, resulting in mutations. Additionally, these agents are toxic to cells at all stages of the cell cycle. Reactive oxygen species (ROS) interact with the building blocks of DNA (including the nitrogenous bases and deoxyribose sugar) resulting in harmful oxidative reactions. These reactions can cause mutations, trigger cell death through apoptosis or necrosis, contribute to the development of cancer, and lead to hereditary diseases. Hydrolytic DNA damage includes processes like deamination, where individual bases are either converted to different bases or completely removed from the DNA strand. When bases are lost entirely, they create AP (apurinic/apyrimidinic) sites, which can cause mutations. If these sites aren't repaired, they can block transcription.