Types of DNA Damage
After DNA has been completely replicated, the daughter strand is often not a perfect copy of the parent strand it came from. Mutations during replication and damage after replication make it necessary for there to be a repair system to fix any errors in newly synthesized DNA. There are three main sources of damage to DNA. Attack by water which can lead to the removal of an amine group from the base group of a nucleotide or the loss of the entire base group. Chemical damage that permanently alters the structure of the DNA. Radiation damage which can lead to nicks in the backbone of DNA or the formation of thymine dimers, which will be discussed later. These different sources of damage lead to different categories of DNA damage. The damage that is caused by water attack can lead to unnatural bases. Chemical and radiation damage leads to the formation of bulky adducts to, or breaks in, the growing DNA strand. In the previous section we discussed the 3' to 5' proof-reading exonuclease that is responsible for fixing mismatches. Because it is not a perfect system, it can miss mismatched bases. As a result, a third category of DNA damage is mismatched bases.
Because these categories of DNA damage are different, there is a need for multiple repair systems. Excision Repair System The first type of repair system we will discuss is the excision repair system. To excise simply means to remove, so this repair systems works by removing the area of damage. Special enzymes recognize damaged DNA. This repair system comes in two forms: Base-excision repair and short-patch nucleotide excision. Base-pair Excision Repair In base-pair excision, single base-pairs are identified and removed. The resultant gap is then filled with a DNA polymerase and the nick is sealed by a DNA ligase. Short-patch Excision Repair Short-patch excision varies from base-pair excision in that its enzymes will recognize and remove "short patches" of DNA that are damaged. These short patches of damage arise from bulky lesions such as thymine dimers. This form of damage is radiation-induced and leads to the formation of a bond between adjacent thymine bases on the same strand of DNA. This bond leads to a distortion in the DNA that makes a short stretch around the thymine dimer unable to base pair correctly. The short-patch excision repair system recognizes such distortions and cuts the damaged strand on both sides of the damaged region leaving a 12 base pair gap in the strand. A helicase then unwinds the stretch of the helix with the damage that can then be filled and sealed with DNA polymerase and ligase. The short-patch excision repair can also be used to correct damage resulting from unnatural bases.