DNA damage

DNA Damage refers to the alterations in the DNA structure of an organism, which can affect its integrity and functionality. These alterations can be in the form of chemical changes to the base pairs, breaks in one or both DNA strands, or cross-links between DNA and other molecules. DNA damage is a major factor in cancer, aging, and various genetic disorders. It can result from environmental factors, such as ultraviolet radiation and chemical carcinogens, or from internal processes like oxidative stress and errors during DNA replication.

Types of DNA Damage

DNA damage can be broadly classified into two categories: endogenous and exogenous damage.

Endogenous Damage

Endogenous damage occurs as a result of normal cellular processes. Examples include:

• Oxidative stress leading to base modifications, particularly of guanine bases, resulting in 8-oxo-2'-deoxyguanosine (8-oxoG).
• DNA replication errors that introduce mismatches or induce strand breaks.

Exogenous Damage

Exogenous damage is caused by external factors, including:

• Ultraviolet (UV) radiation causing cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts.
• Ionizing radiation leading to double-strand breaks (DSBs).
• Chemical carcinogens that form adducts with DNA or cause other structural modifications.

Detection and Repair

Cells have evolved a variety of mechanisms to detect and repair DNA damage. These include:

• Nucleotide excision repair (NER) for UV-induced damage and bulky chemical adducts.
• Base excision repair (BER) for small, non-helix-distorting base lesions.
• Mismatch repair (MMR) for replication errors.
• Homologous recombination (HR) and non-homologous end joining (NHEJ) for double-strand breaks.

Consequences of Unrepaired DNA Damage

If DNA damage is not properly repaired, it can lead to mutations, which may accumulate and result in cancer or other diseases. In addition, severe DNA damage can trigger apoptosis, a process of programmed cell death, to prevent the propagation of damaged DNA.

Prevention

Preventive measures against DNA damage include minimizing exposure to known environmental hazards, such as UV light and carcinogens, and maintaining a healthy lifestyle to reduce oxidative stress. Additionally, some nutrients and antioxidants can help protect DNA by neutralizing reactive oxygen species (ROS).

See Also

• Genotoxicity
• DNA Repair
• Mutagenesis
• Oncogene
• Tumor Suppressor Gene