Endonucleases apurinic/apyrimidinic

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... 

Fujimura M, Moiita-Fujimura Y, Narasimhan P, Copin J, Kawase M, Chan P (1999) Copper-zinc superoxide dismutase prevents the early decrease of apurinic/apyrimidinic endonuclease and subsequent DNA fragmentation after transient focal cerebral ischemia in mice. Stroke... 

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-... 

Nucleotide excision and base removal followed by the action of apurinic-apyrimidine endonucleases (AP endonucleases) are the two types of excision repair that currently are thought to occur. A number of nucleotides are excised from the damaged DNA strand. After excision, the correct complementary bases are replaced by polymerase action, with the intact strand as template. Finally, the new strand is attached covalently to the adjacent undamaged old strand by the enzyme DNA ligase. 

Coordinating the initial steps of base excision repair. Apurinic/ apyrimidinic endonuclease 1 actively stimulates thymine DNA glycosylase by disrupting the product complex. J. Biol. Chem., 283, 32680-32690. 

A damaged base ( ) is excised from the sugar-phosphate backbone by DNA glycosylase, creating an AP site. Then an apurinic/apyrimidinic endonuclease severs the DNA strand, and an excision nuclease removes the AP site and several nucleotides. DNA polymerase I and DNA ligase then repair the gap. 

After a DNA glycosylase excises a lesion base, the resulting product is further processed by an AP (apurinic/apyrimidinic) endonuclease, which nicks the DNA backbone on the 5 side of the lesion base. When an AP endonuclease acts on an abasic site generated by a monofunctional DNA glycosylase, the product is a 5 -deoxyribosephosphate (5 -dRP) group (Fig. 3). This species is usually removed by DNA polymerase j3, the repair polymerase. However, an alternative pathway is sometimes used in which DNA polymerase 6/e, together with PCNA and FEN-1, displaces the strand... 

Mol, C. D., Hosfield, D. J., and Tainer, J. A. (2000a). Abasic site recognition by two apurinic/apyrimidinic endonuclease families in DNA base excision repair The 3 ends justify the means. Mutat. Res. 460, 211-229. 

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

Fig. 3. Reactions catalyzed by apurinic/apyrimidinic (AP) endonucleases. An AP endonuclease will generate a 5 -dRP group and a nicked strand when acting on an abasic site. Alternatively, a single-nucleotide gap will be created if the substrate is the / -elimination product of a bifunctional DNA glycosylase.

FIGURE 3.4 Reaction specificities of E. colt Exo III on dsDNA. Exo III exhibits three types of hydrolytic activities on dsDNA substrates Exo (for 3 — 5 -exonuclease), 3 -phosphatase, and AP endo (for apurinic/apyrimidinic/urea endonuclease). 

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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