AP site
AP Site
An AP site (apurinic/apyrimidinic site) is a location in DNA that has neither a purine nor a pyrimidine base, usually due to DNA damage. These sites are also known as abasic sites. AP sites are critical intermediates in the base excision repair (BER) pathway, which is a cellular mechanism that repairs damaged DNA throughout the cell cycle.
Formation
AP sites are formed when the glycosidic bond between the base and the deoxyribose sugar is cleaved, leaving behind a sugar-phosphate backbone without a base. This can occur spontaneously or as a result of enzymatic activity, such as the action of DNA glycosylases during the BER process.
Repair Mechanism
The repair of AP sites is a crucial step in maintaining genomic stability. The process involves several key steps:
1. Recognition and Cleavage: The AP site is recognized by an AP endonuclease, which cleaves the phosphodiester bond at the 5' end of the abasic site. 2. Removal of the Sugar-Phosphate Residue: The resulting 3' hydroxyl group is then processed by a phosphodiesterase or lyase to remove the sugar-phosphate residue. 3. DNA Synthesis and Ligation: A DNA polymerase fills in the missing nucleotide, and DNA ligase seals the nick in the DNA backbone.
Biological Significance
AP sites are one of the most common forms of DNA damage, occurring at an estimated rate of thousands per cell per day. If left unrepaired, they can lead to mutations or strand breaks, which can contribute to carcinogenesis and other diseases.
AP Lyase Mechanism
AP lyases are enzymes that play a role in the repair of AP sites by cleaving the DNA backbone at the site of damage. The mechanism involves the formation of a covalent intermediate between the enzyme and the DNA, followed by a _-elimination reaction that removes the abasic sugar.
Related Pages
Gallery
Illustration of an AP site in DNA.
Mechanism of AP lyase action on an abasic site.
AP site
AP site
AP lyase mechanism
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