DNA damage refers to changes in the basic structure of DNA, which can occur in a variety of ways and can have significant effects on cell function.
There are several types of DNA damage:
- Base modifications: These include alterations to the chemical structure of the DNA bases themselves. For instance, oxidative stress can lead to the formation of 8-oxoguanine, a modified form of guanine that can pair with adenine instead of cytosine, leading to a mismatch during DNA replication.
- Single-strand breaks (SSBs): These are breaks in one of the two strands of the DNA molecule. They can be caused by factors such as ionizing radiation, oxidative stress, certain chemicals, and some enzymatic activities.
- Double-strand breaks (DSBs): These are breaks in both strands of the DNA molecule, and are considered particularly dangerous because they can lead to large-scale rearrangements of the genome if not repaired correctly. DSBs can be caused by factors such as ionizing radiation, certain chemicals, and errors during DNA replication.
- Crosslinks: These involve connections between DNA strands that are not supposed to be there. They can be intrastrand (within the same strand) or interstrand (between two strands). Crosslinks can interfere with the separation of the DNA strands that is necessary for replication and transcription.
Cells have evolved a variety of DNA repair mechanisms to deal with these types of damage. These include base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and repair of DSBs by homologous recombination or non-homologous end joining.
However, if the damage is too severe or the repair mechanisms are overwhelmed or not functioning properly, DNA damage can lead to mutations, genomic instability, and cell death. In the long term, accumulated DNA damage and mutations can contribute to aging and the development of diseases such as cancer.
