Summary
Highlights
While rare beneficial mutations drive evolution, maintaining DNA integrity is crucial. Defects in DNA repair are linked to premature aging and many cancers, highlighting the vital role of these cellular repair systems.
DNA in each cell is damaged tens of thousands of times daily, leading to quintillions of DNA errors across the body. This damage can disrupt protein blueprints and cause serious problems like cancer.
Damage can manifest as altered nucleotides, incorrect nucleotide pairings (mutations), or breaks in the DNA strands, interfering with replication or rearranging DNA sections.
Cells have specialized enzymes to fix most DNA problems. During replication, DNA polymerase makes errors about once every hundred thousand additions. It, along with a secondary protein team, corrects these base mismatches, reducing errors to about one in one billion.
DNA can be damaged post-replication by various molecules, including environmental toxins like tobacco smoke compounds and natural cellular substances like hydrogen peroxide. Cells have specific and general repair pathways for these chemical changes.
If only one base is damaged, base excision repair is often used. An enzyme snips out the damaged base, and other enzymes replace the surrounding nucleotides, restoring the DNA.
UV light can cause adjacent nucleotides to stick together, distorting the DNA helix. This more complex damage is fixed by nucleotide excision repair, where a team of proteins removes and replaces a long strand of nucleotides.
High-frequency radiation (gamma rays, x-rays) can sever DNA strands. Double-strand breaks are most dangerous, potentially causing cell death. Two main repair pathways are homologous recombination and non-homologous end joining.
Homologous recombination uses an undamaged DNA section as a template to repair breaks accurately. Non-homologous end joining, without a template, trims ends and fuses them, which is less accurate but vital when a template is unavailable. The latter can lead to gene rearrangement.