Base Excision Repair

A base excision repair is a cellular mechanism that is used to repair damaged DNA during the replication of DNA. This is particularly important to ensure that mutations are not induced during this replication.

The main problem with DNA has been that single bases of it can be chemically mutated by deamination or alkylation. This, in turn, may lead to incorrect base pairing and can then result in mutations in the DNA that become perpetuated. The base excision repair involves the flipping of the mutated base out of the DNA helix, and then repairing the base alone. For this, there are two enzymes that are used: DNA glycosylases and AP endonucleases.

[Page 213]The first of these, the DNA glycosylase, has the ability to recognize a number of different damaged bases. It is also able to remove any DNA bases that are cytotoxic or that may cause DNA polymerase to make errors. Some of these DNA glycosylases have been shown to be bifunctional, by displaying a lyase activity. The DNA glycosylase then initiates a base excision repair pathway and this helps with the identification of the damaged DNA structure, or when there is an inappropriate base. Much base excision repair takes place automatically and the human body includes a large number of DNA glycosylases naturally. These include uracil DNA glycosylases, single-strand selective monofunctional uracil-DNA glycosylase (known as SMUG1), and thymine DNA glycosylase (known as TDG). Mention should also be made of the reactive oxygen species (ROS), which is the major source of endogenous DNA damage.