less favorable by linking to the base or the deoxyribose ring. Enzymes, namely DNA glycosylases, also commonly create AP sites, as part of the base excision repair pathway. In a given mammalian cell, 5000–10,000 apurinic sites are estimated to form per day. Apyrimidinic sites form at a rate roughly 20 times slower, with estimates at around 500 formation events per day, per cell. At rates this high, it is critical for cells to have a robust repair apparatus in place in order to prevent mutation. Characteristics Chemical characteristics AP sites are extremely reactive. They fluctuate between a furanose ring and an open-chain free aldehyde and free alcohol conformation. Exposure to a nucleophile can cause a β-elimination reaction, wherein the 3' phosphoester bond is broken, causing a single-stranded break. This reaction can be catalyzed by AP lyase. In the presence of excess reagent, an additional elimination can occur on the 5' side. The free aldehyde can also react with nucleophilic, amine-containing aldehydes. These reactions can further promote phosphoester bond cleavage. Aldehydes containing O-HN2 groups can serve to stabilize the abasic site by reacting with the aldehyde group. This interaction does not cleave the phosphoester bond. Biological activity AP sites in living cells can cause various and severe consequences, including cell death. The single-stranded breaks occurring due to β-elimination require repair by DNA Ligase in order to avoid mutation. When DNA polymerase encounters an abasic site, DNA replication is usually blocked, which may itself lead to a single-stranded or double-stranded break in the DNA helix. In E. coli, when the enzyme manages to bypass the abasic site, an adenine is preferentially incorporated into the new strand. If AP sites in DNA are not repaired, DNA replication cannot proceed normally, and significant mutations can result. If mutations are merely single nucleotide polymorphisms, then the cell can potentially be unaffected. However, if more serious mutations occur, cell function can be severely impaired, growth and division may be impaired, or the cell may simply die. Repair AP sites are an important feature of the base excision repair pathway. DNA glycosylases first create abasic sites by recognizing and removing modified bases. Many glycosylase variants exist to deal with the multiple ways a base can be damaged. The most common circumstances are base alkylation, oxidation, and the presence of a uracil in the DNA strand. Once an AP site has been successful created, an AP endonuclease catalyzes