8.9 : Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.

Chemically modified genomic DNA can cause errors during transcription and translation into proteins. If the damaged DNA is not repaired before cell division, the genomic mutations can be transferred to the next generations of cells. Some of these mutations can lead to uncontrolled cell growth that develops into cancer.

The cell has developed robust systems to detect and repair DNA damage. DNA damage can be repaired by enzymes that can directly reverse the chemical change in a single reaction. For example, enzyme photolyase uses UV radiation to split thymine dimers by opening the cyclobutane moiety that holds the thymine dimer together.

Other forms of repair follow a multi-step process in which

1. Chemical modifications in the DNA are detected
2. Damaged base or region is removed
3. New DNA is synthesized

If the damage is beyond repair, the cell can either become senescent or undergo apoptosis. Senescence is a state in which the cell becomes irreversibly dormant, i.e., it can no longer undergo cell division, and its cell cycle is halted indefinitely. Apoptosis refers to programmed cell death, where proteins called caspases degrade the cellular components required for cell survival. This is followed by the digestion of DNA by DNases, which causes the cell to shrink in size and transmit signals to a group of white blood cells called macrophages, which engulf and remove cellular debris.