Apurinic/apyrimidinic

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. 

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... 

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... 

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... 

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. 

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. 

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

Aburatani, H., Hippo, Y, IsJucta, T.. Takashima, R., Matsuba, C., Kodama, T., Takao, M., Yasui, A., Yamamoto, K, Asa no, M., Fukasawa, K., Yoshinart, T., Inoue, H., Ohtsuka, E, and Nishimura, ft. (1997). Cloning and characterization of mammalian 8-hydroxy-guanini -specific DNA glycosylase/apurinic, apyrimidinic lyase. Cancer Res. 57, 2151-2156,... 

Sagher, D. and Strauss, B. (1983) Insertion of nucleotides opposite apurinic/apyrimidinic sites in deoxyribonucleic acid during in vitro synthesis. Uniqueness of adenine nucleotides. Biochemistry, 22,4518-4526. 

P.B., Chiang, S.Y., Row, Y.W., and Swenberg, J.A. (1998) Highly sensitive apurinic/apyrimidinic site assay can detect spontaneous and chemically induced depurination under physiological conditions. Cancer Res., 58, 222-225. 

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. 

R. D. (2005) DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/ apyrimidinic sites, and compound lesions in DNA. J. Biol. Chem., 280, 39982-39989. 

P.B., Chiang, S.Y., Row, Y.W., and Swenberg, J.A. (1998) Highly sensitive apurinic/apyrimidinic site assay can detect spontaneous and chemically induced depurination under physiological conditions. Cancer Res., 58, 222-225. Loeb, L.A. and Preston, B.D. (1986) Mutagenesis by apurinic/apyrimidinic sites. Annu. Rev. Genet., 20, 201-230. Xue, L. and Greenberg, M.M. (2007)... 

Kokoska, R.J., McCulloch, S.D., and Kunkel, T.A. (2003) The efficiency and specificity of apurinic/apyrimidinic site bypass by human DNA polymerase r and Sulfolobus solfataricus Dpo4. J. Biol. Chem., 278, 50537-50545. 

Figure 16.4 DNA lesions used in TLS studies with gapped plasmids. BP-G, B[o]P-guanine adduct AP site, apurinic/apyrimidinic site 4-OHEN-C, 4-hydroxyequilenin-C adduct M12, dodecamethylene Cisplatin-GG, c/s-diamminedichloroplatinum(ll)-GG intrastrand crosslink ...

Until recently, all enzymes that catalyze the cleavage of phosphate ester bonds were assumed to be phosphohydrolases, i.e., the cleavage reaction occurs by hydrolysis of a phosphodiester bond to generate ends containing a phosphate monoester and a hydroxyl group. This assumption has now been shown to be incorrect for enzymes that introduce strand breaks on the 3 -side of aldehydic abasic sites (also referred to as apurinic, apyrimidinic, or simply AP sites) during DNA repair. Despite the title of this chapter, the mechanism of the strand cleavage reaction will be briefly described. 

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