Apyrimidinic/apurinic site

The production of apurinic and apyrimidinic sites can both be caused by alkylating agents. When, for example, the N7 of guanine is alkylated, this causes the bond from base to sugar to become labile and so the base can be lost completely. Thus, apurinic sites are formed. Insertion of an incorrect base at this site can then cause a mutation. Loss of purines and pyrimidines can also occur spontaneously. 

This leaves an AP site (where AP stands for apurinic or apyrimidinic). This site may become occupied by a different base, leading again to alteration of DNA. 

Insertases Catalyze the reinsertion of a missing base into the appropriate apurinic or apyrimidinic AP sites of DNA. 

Glycosylases Catalyze hydrolysis of nucleoside bases-glycosidic bonds, resulting in production of an apurinic/ apyrimidinic (AP) site in DNA and a free nucleoside base ... 

Recently, Sage and Haseltine (49) have quantitatively determined the spectrum of DNA lesions induced by reactions of BPDE with DNA. They found that alkali-labile lesions account for about 40% of the DNA adducts. There was a striking correlation between the mutation frequencies induced by BPDE in lacl and the frequencies of alkali sensitive lesions at G, A, and C residues. Apurinic/apyrimidinic sites are common alkali-sensitive lesions. Earlier work by Drink-water e al. (48) had also shown that treatment of DNA with BPDE generated apurinic/apyrimidinic sites. 

Lindahl, T. (1979). DNA glycoslylases, endonucleases for apurinic/apyrimidinic sites and base excision repair. Proc. Nuc. Acid Res. Mol. Biol. 22 109-118. 

Deoxyribonuclease V [EC 3.1.22.3], also known as endodeoxyribonuclease V, catalyzes the endonucleolytic cleavage of DNA at apurinic or apyrimidinic sites to products with a 3 -phosphate. 

DNA-(apurinic or apyrimidinic site) lyase [EC 4.2.99.18, formerly EC 3.1.25.2] acts on the C-Q-P bond 3 to the apurinic or apyrimidinic site in DNA. This bond is broken by a /3-elimination reaction, leaving a 3 -terminal unsaturated sugar and a product with a terminal 5 -phosphate. Note that this nicking of the phosphodiester bond is a lyase-type reaction, not hydrolysis. 

This apurinic/apyrimidinic endonuclease from E. coli catalyzes the hydrolysis of single-stranded polydeoxyri-bonucleotides and DNA that contains depyrimidinic sites. 

Mg apurinic/apyrimidinic endonuclease 1 Mg APEl Site 1 Site 2... 

A glycosylase enzyme recognizes and removes the damaged base to give an apurinic or apyrimidinic site. 

Apurinic/apyrimidinic site production in SV40 DNA in vitro + NT 2.0 Drinkwater ei a/. (1980)... 

Drinkwater, N.R.. Miller. E.C. Miller, J.A. (1980) Estimation of apurinic/apyrimidinic sites and phosphotriesters in deoxyribonucleic acid treated with electrophilic carcinogens and mutagens. Biochemistry, 19, 5087-5092... 

Base-Excision Repair Every cell has a class of enzymes called DNA glycosylases that recognize particularly common DNA lesions (such as the products of cytosine and adenine deamination see Fig. 8-33a) and remove the affected base by cleaving the Af-glycosyl bond. This cleavage creates an apurinic or apyrimidinic site in the DNA, commonly referred to as an AP site or abasic... 

Removal of abnormal bases Abnormal bases, such as uracil, which can occur in DNA either by deamination of cytosine or improper incorporation of dUTP instead of dTTP during DNA synthesis, are recognized by specific glycosylases that hydrolytically cleave them from the deoxyribose-phosphate backbone of the strand. This leaves an apyrimidinic site (or apurinic, if a purine was removed), referred to as an AP-site. 

As the word suggests, an abasic site (apurinic/apyrimidinic site, AP) lacks the base, but the DNA backbone is more or less intact. The simplest AP is a 2-dR site, formed... 

Chaudry MA, Weinfeld M (1997) Reactivity of human apurinic/apyrimidinic endonuclease and Escherichia coli exonulcease III with bistranded abasic sites in DNA. J Biol Chem 272 15650-15655 Chaudry MA, Dedon PC, Wilson DM III, Demple B, Weinfeld M (1999) Removal by human apurinic/ apyrimidinic endonuclease 1 (Ape 1) and Escherichia coli exonuclease III of 3 -phosphoglyco-... 

Apurinic/apyrimidinic site containing a 2-deoxyribonolactone unit Double-stranded Double-strand break Double-stranded DNA... 

Fresco P, Shacker F, Kortenkamp A. 1995. The reductive conversion of chromium (VI) by ascorbate gives rise to apurinic/apyrimidinic sites in isolated DNA. Chem Res Toxicol 8 884-890. 

The removal of an altered base by the glycosylase results in the formation of an abasic site (AP site) (sometimes also referred to as an apurinic or apyrimidinic site). The AP site is acted upon by an AP endonuclease that makes an incision in the damaged strand by hydrolyzing the phosphodiester bond 5 to the AP site (Figure 23.5). Alternatively, some glycosylases have an associated lyase activity that incises... 

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