Base Excision Repair

Base excision repair (BER) is a process that removes one or more nucleotides from a site of base damage. The process initiates with enzymatic cleavage of the glycosidic bond between the damaged base and deoxyribose. The replacement of uracil by thymine in DNA by uracil-DNA N-glycosylase (see here) is an example of BER. Figure 25.13 illustrates BER of a thymine dimer (see here), as initiated by endonuclease V of bacteriophage T4. This enzyme has two activities, a glycosylase and an AP endonuclease. The glycosylase cleaves between the thymine on the 5' side of the dimer and its associated deoxyribose. The AP endonuclease, on the other hand, recognizes the apyrimidinic (AP) site, consisting of a deoxyribose without an associated pyrimidine base, and cleaves on its 5' side.

A second cleavage, 3' to that site, by deoxyribophosphodiesterase, releases deoxyribose-5-phosphate. Next, nick translation by DNA polymerase I, followed by DNA ligase, replaces the damaged DNA and closes the nick.

BER often involves separate enzymes for glycosidic cleavage and endonucleolytic cleavage of the abasic site (apyrimidinic or apurinic, depending on the damage).

Most cells contain several DNA-N-glycosylases.

Oxidative damage to DNA is repaired primarily by BER. The oxidized base 8-oxoguanine, for example, can be removed from DNA by the protein products of the E. coli mutM and mutY genes. The MutM protein removes 8-oxoguanine (and other oxidized bases), while the MutY protein removes adenine that is mispaired to 8-oxoG (Figure 25.14).

See also: Nucleotide Excision Repair, Types and Consequences of DNA Damage

INTERNET LINK: DNA Repair