DNA damage can occur due to a variety of factors, including exposure to radiation, chemicals, and reactive oxygen species. These can cause changes in the DNA sequence or structure, including single-strand breaks, double-strand breaks, and modifications to individual nucleotides.
To maintain the integrity of the genetic information, cells have several mechanisms for repairing damaged DNA. The three main types of DNA repair mechanisms are:
- Base excision repair (BER): This mechanism repairs DNA damage caused by the loss of a single base or a modified base. Specific enzymes recognize and remove the damaged base, leaving an abasic site. The site is then filled with the correct nucleotide by DNA polymerase and sealed by a DNA ligase.
- Nucleotide excision repair (NER): This mechanism repairs damage that distorts the DNA helix, such as bulky chemical adducts or UV-induced thymine dimers. A complex of enzymes recognizes the damage and cleaves the DNA strand on either side of the damage, removing a short stretch of nucleotides. The gap is then filled with the correct nucleotides by DNA polymerase and sealed by DNA ligase.
- Mismatch repair (MMR): This mechanism corrects errors that occur during DNA replication, such as misincorporation of incorrect nucleotides or slippage of the replication machinery. Mismatch repair proteins recognize and remove the mismatched nucleotide, along with a stretch of surrounding nucleotides. The gap is then filled with the correct nucleotides by DNA polymerase and sealed by DNA ligase.
In addition to these mechanisms, cells also have the ability to repair double-strand breaks in DNA through two main pathways:
- Non-homologous end joining (NHEJ): This mechanism repairs double-strand breaks by directly ligating the broken ends of the DNA back together. This pathway can lead to loss or rearrangement of genetic information at the site of the break.
- Homologous recombination (HR): This mechanism repairs double-strand breaks by using a homologous sequence as a template for repair. The broken DNA strand is resected to create a single-stranded overhang that invades a homologous DNA molecule. The invading strand is then used as a template to repair the broken strand, resulting in accurate repair of the double-strand break.
These DNA repair mechanisms are essential for maintaining the integrity of the genetic information and preventing the accumulation of mutations that can lead to cancer and other genetic diseases.