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][2]
AP sites can be formed by spontaneous depurination, but also occur as intermediates in base excision repair.[3] 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 deoxyribose-5-phosphate 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.[4]
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.[3]
^Tropp, Burton (2012). Molecular Biology. Sudbury, MA: Jones & Bartlett Learning. p. 455. ISBN 978-1-4496-0091-4.
^Borlé, Myriam (1987). "Formation, detection, and repair of AP sites". Mutation Research. 181 (1): 45–56. doi:10.1016/0027-5107(87)90286-7. PMID 2444877.
^ abAbasic sites in DNA: repair and biological consequences in Saccharomyces cerevisiae. DNA Repair (Amst). 2004 Jan 5;3(1):1-12.
^Lindhal, Tomas (1993). "Instability and decay of the primary structure of DNA". Nature. 362 (6422): 709–715. Bibcode:1993Natur.362..709L. doi:10.1038/362709a0. PMID 8469282. S2CID 4283694.
In biochemistry and molecular genetics, an APsite (apurinic/apyrimidinic site), also known as an abasic site, is a location in DNA (also in RNA but much...
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phosphodiester backbone of the APsite created when DNA glycosylase removes the damaged base. There are four types of AP endonucleases that have been classified...
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and 5caC and excises the glycosidic bond resulting in an apyrimidinic site (APsite). In an alternative oxidative deamination pathway, 5hmC can be oxidatively...
remove specific damaged or inappropriate bases, forming APsites. These are then cleaved by an AP endonuclease. The resulting single-strand break can then...
apyrimidinic site) lyase is an enzyme that in humans is encoded by the APEX1 gene. Apurinic/apyrimidinic (AP) sites (also called "abasic sites") occur frequently...
uracil-DNA glycosylase, generating an abasic (AP) site. The resulting abasic site is then recognised by enzymes (AP endonucleases) that break a phosphodiester...
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Endonucleases play a role in DNA repair. AP endonuclease, specifically, catalyzes the incision of DNA exclusively at APsites, and therefore prepares DNA for subsequent...
the CpG site with a methylated cytosine. After an APsite is formed, AP endonuclease creates a nick in the phosphodiester backbone of the APsite that was...
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enzyme specific for pyrimidine dimers. It is then able to cut open the APsite. Another type of repair mechanism that is conserved in humans and other...
sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an APsite. This is accomplished by flipping the damaged base out...
and 5caC and excises the glycosidic bond resulting in an apyrimidinic site (APsite). In an alternative oxidative deamination pathway, 5hmC can be oxidatively...
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