AP site
In biochemistry and molecular genetics, an AP site (apurinic/apyrimidinic site), also known as an abasic site, is a location in DNA (also in RNA but much less likely) that has neither a purine nor a pyrimidine base, either spontaneously or due to DNA damage. It has been estimated that under physiological conditions 10,000 apurinic sites and 500 apyrimidinic may be generated in a cell daily.[1]
AP sites can be formed by spontaneous depurination, but also occur as intermediates in base excision repair.[2] In this process, a DNA glycosylase recognizes a damaged base and cleaves the N-glycosidic bond to release the base, leaving an AP site. A variety of glycosylases that recognize different types of damage exist, including oxidized or methylated bases, or uracil in DNA. The AP site can then be cleaved by an AP endonuclease, leaving 3' hydroxyl and 5' deoxyribosephosphate termini (see DNA structure). In alternative fashion, bifunctional glycosylase-lyases can cleave the AP site, leaving a 5' phosphate adjacent to a 3' α,β-unsaturated aldehyde. Both mechanisms form a single-strand break, which is then repaired by either short-patch or long-patch base excision repair.
If left unrepaired, AP sites can lead to mutation during semiconservative replication. They can cause replication fork stalling and are bypassed by translesion synthesis. In E. coli, adenine is preferentially inserted across from AP sites, known as the "A rule". The situation is more complex in higher eukaryotes, with different nucleotides showing a preference depending on the organism and experimental conditions.[2]
References
- ↑ Tropp, Burton (2012). Molecular Biology. Sudbury, MA: Jones & Bartlett Learning. p. 455. ISBN 978-1-4496-0091-4.
- 1 2 Abasic sites in DNA: repair and biological consequences in Saccharomyces cerevisiae. DNA Repair (Amst). 2004 Jan 5;3(1):1-12.