apurinic acid

Summary

Summary: Hydrolysate of DNA in which purine bases have been removed.

Top Publications

  1. de Los Santos C, El Khateeb M, Rege P, Tian K, Johnson F. Impact of the C1' configuration of abasic sites on DNA duplex structure. Biochemistry. 2004;43:15349-57 pubmed
    ..Our results challenge the suggestion that Ape1 is stereoselective and imply a plasticity at the active site of the enzyme for accommodating either anomer of the lesion. ..
  2. Ilina E, Khodyreva S, Berezhnoy A, Larin S, Lavrik O. Tracking Ku antigen levels in cell extracts with DNA containing abasic sites. Mutat Res. 2010;685:90-6 pubmed publisher
    ..As a routine test, borohydride trapping (BHT) is also less time and reagent consuming than blotting and EMSA. ..
  3. Bjoras M, Luna L, Johnsen B, Hoff E, Haug T, Rognes T, et al. Opposite base-dependent reactions of a human base excision repair enzyme on DNA containing 7,8-dihydro-8-oxoguanine and abasic sites. EMBO J. 1997;16:6314-22 pubmed
  4. Rodriguez Y, Smerdon M. The structural location of DNA lesions in nucleosome core particles determines accessibility by base excision repair enzymes. J Biol Chem. 2013;288:13863-75 pubmed publisher
    ..Therefore, remodeling at DNA damage sites in NCPs is critical for preventing accumulation of aborted intermediates and ensuring completion of base excision repair. ..
  5. Bailly V, Verly W. Importance of thiols in the repair mechanisms of DNA containing AP (apurinic or apyrimidinic) sites. Nucleic Acids Res. 1988;16:9489-96 pubmed
    ..In living cells, thiols might influence the pathways followed by the repair processes of AP site-containing DNA. ..
  6. Yu H, Zhang X, Liu R, Li H, Xiao X, Zhou Y, et al. Mcl-1 suppresses abasic site repair following bile acid-induced hepatic cellular DNA damage. Tumour Biol. 2017;39:1010428317712102 pubmed publisher
    ..These results potentially explain how bile acid accumulation results in genetic instability and carcinogenesis. ..
  7. Monti P, Broxson C, Inga A, Wang R, Menichini P, Tornaletti S, et al. 3-Methyl-3-deazaadenine, a stable isostere of N3-methyl-adenine, is efficiently bypassed by replication in vivo and by transcription in vitro. DNA Repair (Amst). 2011;10:861-8 pubmed publisher
    ..We conclude that, in these experimental systems, 3-m-c(3)A is efficiently bypassed by replication in vivo and by transcription in vitro. ..
  8. Admiraal S, O Brien P. DNA-N-glycosylases process novel O-glycosidic sites in DNA. Biochemistry. 2013;52:4066-74 pubmed publisher
    ..Although the biological significance of the DNA-O-glycosidase reactions is not known, the evolution of new DNA repair pathways may be aided by enzymes that practice catalytic promiscuity, such as these two unrelated DNA glycosylases. ..
  9. Bailly V, Verly W, O CONNOR T, Laval J. Mechanism of DNA strand nicking at apurinic/apyrimidinic sites by Escherichia coli [formamidopyrimidine]DNA glycosylase. Biochem J. 1989;262:581-9 pubmed
    ..The enzyme is without action on a 3'-terminal base-free deoxyribose or on a 3'-terminal base-free unsaturated sugar produced by a beta-elimination reaction nicking the DNA strand 3' to an apurinic or apyrimidinic site. ..

More Information

Publications62

  1. Rossi O, Filiberti R, Neri M, Biggi S, Satragno L, Puntoni R, et al. Incision of AP sites in lung cancer patients: a pilot study. Teratog Carcinog Mutagen. 2002;22:251-6 pubmed
    ..Unlike other BER enzymatic steps, marked defects in incision of AP sites may not be associated with lung carcinogenesis. ..
  2. Deutsch W, Hegde V. Analysis of DNA strand cleavage at abasic sites. Methods Mol Biol. 2005;291:39-46 pubmed
    ..Here we describe a method for analyzing the manner in which repair endonucleases differ in the way they create nicks in DNA and how to distinguish between them using cellular crude extracts. ..
  3. Cavalieri E, Rogan E, Li K, Todorovic R, Ariese F, Jankowiak R, et al. Identification and quantification of the depurinating DNA adducts formed in mouse skin treated with dibenzo[a,l]pyrene (DB[a,l]P) or its metabolites and in rat mammary gland treated with DB[a,l]P. Chem Res Toxicol. 2005;18:976-83 pubmed
    ..Only one depurinating diol epoxide adduct was formed. Tumorigenicity, mutations, and DNA adduct data suggest that depurinating Ade adducts play a major role in the initiation of tumors by DB[a,l]P. ..
  4. Sczepanski J, Wong R, McKnight J, Bowman G, Greenberg M. Rapid DNA-protein cross-linking and strand scission by an abasic site in a nucleosome core particle. Proc Natl Acad Sci U S A. 2010;107:22475-80 pubmed publisher
    ..These results show that AP sites within the nucleosome produce significant amounts of DNA-protein cross-links and generate double strand breaks, the most deleterious form of DNA damage. ..
  5. Barsky D, Foloppe N, Ahmadia S, Wilson D, MacKerell A. New insights into the structure of abasic DNA from molecular dynamics simulations. Nucleic Acids Res. 2000;28:2613-26 pubmed publisher
    ..The data indicate that abasic DNA contorts more easily and in specific ways relative to unmodified DNA, an aspect likely to be important in abasic site recognition and hydrolysis. ..
  6. Petty A, Dick C, Lindsey J. Translation of an atypical human cDNA requires fidelity of apurine-pyrimidine repeat region and recoding. Gene. 2008;414:49-59 pubmed publisher
    ..In this report, we detail requirements for cloning and expression of this novel, atypical, human gene. These techniques can be used to express this unique protein for further studies. ..
  7. Frosina G, Cappelli E, Ropolo M, Fortini P, Pascucci B, Dogliotti E. In vitro base excision repair assay using mammalian cell extracts. Methods Mol Biol. 2006;314:377-96 pubmed
    ..The construction of a single lesion at a defined site of the plasmid genome makes the substrate amenable to fine mapping of the repair patches, thus allowing discrimination between the two BER pathways...
  8. Krokan H, Otterlei M, Nilsen H, Kavli B, Skorpen F, Andersen S, et al. Properties and functions of human uracil-DNA glycosylase from the UNG gene. Prog Nucleic Acid Res Mol Biol. 2001;68:365-86 pubmed
    ..We propose that BER is important both in the prevention of cancer and for preserving the integrity of germ cell DNA during evolution. ..
  9. Allinson S, Sleeth K, Matthewman G, Dianov G. Orchestration of base excision repair by controlling the rates of enzymatic activities. DNA Repair (Amst). 2004;3:23-31 pubmed
    ..However, during repair of the apurinic/apyrimidinic (AP) sites or 5,6-dihydrouracil, poly(ADP-ribose) polymerase plays an important role in the coordination of the rates of repair reactions. ..
  10. Demple B, Sung J. Molecular and biological roles of Ape1 protein in mammalian base excision repair. DNA Repair (Amst). 2005;4:1442-9 pubmed
    ..Notably, all these effects are reversed by expression of the unrelated protein Apn1 of S. cerevisiae, which shares only the enzymatic repair function with Ape1 (AP endonuclease). ..
  11. Jaiswal A, Panda H, Pampo C, Siemann D, Gairola C, Hromas R, et al. Adenomatous polyposis coli-mediated accumulation of abasic DNA lesions lead to cigarette smoke condensate-induced neoplastic transformation of normal breast epithelial cells. Neoplasia. 2013;15:454-60 pubmed
  12. Kingma P, Osheroff N. Apurinic sites are position-specific topoisomerase II poisons. J Biol Chem. 1997;272:1148-55 pubmed
    ..A model is proposed that encompasses the actions of endogenous and exogenous topoisomerase II poisons and provides a pre-existing pathway for the cellular actions of topoisomerase II-targeted anticancer drugs. ..
  13. Chapman K, Cavalieri E, Rogan E. Repair of short oligodeoxyribonucleotides containing a stable adduct and an apurinic site by extracts of MCF-10A1 cells. Anticancer Res. 2004;24:117-21 pubmed
    ..The ability of human breast MCF-10A1 cells to repair DNA adducts and AP sites is affected by other near-by lesions. ..
  14. Hendricks C, Razlog M, Matsuguchi T, Goyal A, Brock A, Engelward B. The S. cerevisiae Mag1 3-methyladenine DNA glycosylase modulates susceptibility to homologous recombination. DNA Repair (Amst). 2002;1:645-59 pubmed
    ..Thus, too little Mag1 sensitizes cells to methylation-induced recombination, while too much Mag1 can put cells at risk of recombination induced by single strand breaks formed during BER. ..
  15. Stone J, Kumar D, Binz S, Inase A, Iwai S, Chabes A, et al. Lesion bypass by S. cerevisiae Pol ζ alone. DNA Repair (Amst). 2011;10:826-34 pubmed publisher
    ..The results are consistent with the hypothesis that, in addition to extending aberrant termini created by other DNA polymerases, Pol ζ has the potential to be the sole DNA polymerase involved in TLS. ..
  16. Shen J, Loeb L. Mutations in the alpha8 loop of human APE1 alter binding and cleavage of DNA containing an abasic site. J Biol Chem. 2003;278:46994-7001 pubmed
    ..This initial mutational analysis of the alpha8 loop supports and extends the conclusion of crystallographic studies that the loop is important for binding of AP.DNA and AP site incision. ..
  17. Greenberg M, Weledji Y, Kroeger K, Kim J. In vitro replication and repair of DNA containing a C2'-oxidized abasic site. Biochemistry. 2004;43:15217-22 pubmed
  18. Dalhus B, Nilsen L, Korvald H, Huffman J, Forstr m R, McMurray C, et al. Sculpting of DNA at abasic sites by DNA glycosylase homolog mag2. Structure. 2013;21:154-166 pubmed publisher
    ..Consequently, the molecular role of Mag2 appears to be AP site recognition and protection, while possibly facilitating damage signaling by structurally sculpting the DNA substrate...
  19. Georgakilas A, Bennett P, Sutherland B. High efficiency detection of bi-stranded abasic clusters in gamma-irradiated DNA by putrescine. Nucleic Acids Res. 2002;30:2800-8 pubmed
    ..Further comparison of PUTR and Nfo protein cleavage may provide useful information on abasic cluster levels and configurations induced by ionizing radiation. ..
  20. Yang H, Clendenin W, Wong D, Demple B, Slupska M, Chiang J, et al. Enhanced activity of adenine-DNA glycosylase (Myh) by apurinic/apyrimidinic endonuclease (Ape1) in mammalian base excision repair of an A/GO mismatch. Nucleic Acids Res. 2001;29:743-52 pubmed
    ..Consequently, Ape1 preserves the Myh preference for A/GO over A/G and improves overall glycosylase efficiency. Our study suggests that protein-protein interactions may occur in vivo to achieve efficient BER of A/GO. ..
  21. Evans R, Xu Z, Bohannon K, Wang B, Bruner M, Volkin D. Evaluation of degradation pathways for plasmid DNA in pharmaceutical formulations via accelerated stability studies. J Pharm Sci. 2000;89:76-87 pubmed
    ..The ability to predict plasmid DNA storage stability in the absence of free radical oxidation should prove to be a valuable tool for the design of stable pharmaceutical formulations of plasmid DNA. ..
  22. Sagi J, Guliaev A, Singer B. 15-mer DNA duplexes containing an abasic site are thermodynamically more stable with adjacent purines than with pyrimidines. Biochemistry. 2001;40:3859-68 pubmed
    ..This work showed that for an AP site the GC content is not the only determinant of duplex stability, but rather is influenced more by whether purines or pyrimidines flank the AP site. ..
  23. Berdis A. Dynamics of translesion DNA synthesis catalyzed by the bacteriophage T4 exonuclease-deficient DNA polymerase. Biochemistry. 2001;40:7180-91 pubmed
    ..Extension from the G:abasic or A:abasic site mispair generates significant elemental effects (between 5 and 20) and suggests that chemistry is at least partially rate-limiting for extension beyond either mispair. ..
  24. Atamna H, Cheung I, Ames B. A method for detecting abasic sites in living cells: age-dependent changes in base excision repair. Proc Natl Acad Sci U S A. 2000;97:686-91 pubmed
    ..The decline in excision of methylated bases from DNA suggests an age-dependent decline in 3-methyladenine DNA glycosylase, a BER enzyme responsible for removing alkylated bases. ..
  25. Tanaka M, Han S, Song H, Küpfer P, Leumann C, Sonntag W. An assay for RNA oxidation induced abasic sites using the Aldehyde Reactive Probe. Free Radic Res. 2011;45:237-47 pubmed publisher
    ..These results indicate the versatility of the assay method for biologically relevant oxidation of RNA. Thus, this study developed a sensitive assay for analysis of oxidized RNA. ..
  26. Hwang H, Taylor J. Role of base stacking and sequence context in the inhibition of yeast DNA polymerase eta by pyrene nucleotide. Biochemistry. 2004;43:14612-23 pubmed
    ..Thus, pyrene nucleotide represents a novel class of nucleotide-based chain-terminating DNA synthesis inhibitors whose base portion consists of a hydrophobic, non-hydrogen bonding, base-pair mimic. ..
  27. Hartley M, Legname G, Osborn R, Chen Z, Lord J. Single-chain ribosome inactivating proteins from plants depurinate Escherichia coli 23S ribosomal RNA. FEBS Lett. 1991;290:65-8 pubmed
    ..The position of the modification of 23S rRNA by dianthin 32 was determined by primer extension and found to be A2660, which lies in a sequence that is highly conserved in all species. ..
  28. Lebedeva N, Rechkunova N, Ishchenko A, Saparbaev M, Lavrik O. The mechanism of human tyrosyl-DNA phosphodiesterase 1 in the cleavage of AP site and its synthetic analogs. DNA Repair (Amst). 2013;12:1037-42 pubmed publisher
    ..The following repair of 5'-THF and other AP-site analogs can be processed by the long-patch base excision repair pathway. ..
  29. Puyet A, Greenberg B, Lacks S. The exoA gene of Streptococcus pneumoniae and its product, a DNA exonuclease with apurinic endonuclease activity. J Bacteriol. 1989;171:2278-86 pubmed
    ..coli, with 26% identity of amino acid residues in the predicted proteins. So far, no null chromosomal mutants of exoA have been obtained, and the biological function of ExoA remains unknown...
  30. Dianov G, Sedgwick B, Daly G, Olsson M, Lovett S, Lindahl T. Release of 5'-terminal deoxyribose-phosphate residues from incised abasic sites in DNA by the Escherichia coli RecJ protein. Nucleic Acids Res. 1994;22:993-8 pubmed
    ..Nevertheless, E. coli fpg recJ double mutants retain capacity to repair abasic sites in DNA, indicating the presence of a back-up excision function. ..
  31. Adhikary S, Cato M, McGary K, Rokas A, Eichman B. Non-productive DNA damage binding by DNA glycosylase-like protein Mag2 from Schizosaccharomyces pombe. DNA Repair (Amst). 2013;12:196-204 pubmed publisher
    ..This work provides novel insight into the chemical and physical determinants by which the HhH glycosylases engage DNA in a catalytically productive manner. ..
  32. Zhao H, Shen J, Deininger P, Hunt J. Abasic sites and survival in resected patients with non-small cell lung cancer. Cancer Lett. 2007;246:47-53 pubmed
    ..We postulate that an intact BER mechanism may reduce the accumulation of oxidative DNA damage that are thought to contribute to the tumor's malignant potential and therefore the risk of death. ..
  33. Wu X, Wang Z. Relationships between yeast Rad27 and Apn1 in response to apurinic/apyrimidinic (AP) sites in DNA. Nucleic Acids Res. 1999;27:956-62 pubmed
    ..In contrast, nucleotide excision repair and BER of oxidative damage were not affected in rad27 mutant extracts, indicating that Rad27 is specifically required for BER of AP sites in DNA. ..
  34. Gunhouse B, Milligan J, Archer M. Interaction of alpha-acetoxy-N-nitrosopyrrolidine with DNA assessed by loss of restriction endonuclease recognition sites and formation of apurinic/apyrimidinic sites. Carcinogenesis. 1988;9:1595-7 pubmed
    ..The recognition sequences of these restriction enzymes suggest that AcO-NPYR interacts preferentially with guanine and/or cytosine bases in DNA. ..
  35. Tanaka M, Jaruga P, Küpfer P, Leumann C, Dizdaroglu M, Sonntag W, et al. RNA oxidation catalyzed by cytochrome c leads to its depurination and cross-linking, which may facilitate cytochrome c release from mitochondria. Free Radic Biol Med. 2012;53:854-62 pubmed publisher
    ..Thus, RNA oxidation may facilitate the release of cyt c from the mitochondrial membrane to induce apoptosis in response to oxidative stress. ..
  36. Deutsch W, Hegde V. Characterization of enzymes that initiate base excision repair at abasic sites. Methods Mol Biol. 2006;314:355-64 pubmed
    ..Here we describe a method for analyzing the manner in which repair endonucleases differ in the way they create nicks in DNA and how to distinguish between them using cellular crude extracts. ..
  37. Bailly V, Derydt M, Verly W. Delta-elimination in the repair of AP (apurinic/apyrimidinic) sites in DNA. Biochem J. 1989;261:707-13 pubmed
    ..These repair pathways, involving a delta-elimination step, may be operational not only in E. coli repairing its DNA containing a formamido-pyrimidine lesion, but also in mammalian cells repairing their nuclear DNA containing AP sites. ..
  38. Matsumoto Y. Molecular mechanism of PCNA-dependent base excision repair. Prog Nucleic Acid Res Mol Biol. 2001;68:129-38 pubmed
    ..Therefore, UNG2 and MYH may serve for replication-coupled base excision repair through the direct interaction with PCNA in the replication machinery. ..
  39. Garcia Gomez S, Reyes A, Martinez Jimenez M, Chocron E, Mouron S, Terrados G, et al. PrimPol, an archaic primase/polymerase operating in human cells. Mol Cell. 2013;52:541-53 pubmed publisher
  40. Cavalieri E, Li K, Balu N, Saeed M, Devanesan P, Higginbotham S, et al. Catechol ortho-quinones: the electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases. Carcinogenesis. 2002;23:1071-7 pubmed
    ..These data suggest that there is a unifying molecular mechanism, namely, formation of specific depurinating DNA adducts at the N-7 of guanine and N-3 of adenine, that could initiate many cancers and neurodegenerative diseases. ..
  41. Sun L, Zhang K, Zhou L, Hohler P, Kool E, Yuan F, et al. Yeast pol eta holds a cis-syn thymine dimer loosely in the active site during elongation opposite the 3'-T of the dimer, but tightly opposite the 5'-T. Biochemistry. 2003;42:9431-7 pubmed
    ..Overall, the results show a marked difference from similar studies on pol I family polymerases, and suggest mechanisms by which this Y family polymerase can process damaged DNA efficiently. ..
  42. Silber J, Bobola M, Blank A, Schoeler K, Haroldson P, Huynh M, et al. The apurinic/apyrimidinic endonuclease activity of Ape1/Ref-1 contributes to human glioma cell resistance to alkylating agents and is elevated by oxidative stress. Clin Cancer Res. 2002;8:3008-18 pubmed
    ..Our results may also be relevant to the design of therapeutic regimens using concurrent ionizing radiation (a generator of ROS) and alkylating agent-based chemotherapy. ..
  43. Wilson V, Jones P. Inhibition of DNA methylation by chemical carcinogens in vitro. Cell. 1983;32:239-46 pubmed
  44. Castaing B, Boiteux S, Zelwer C. DNA containing a chemically reduced apurinic site is a high affinity ligand for the E. coli formamidopyrimidine-DNA glycosylase. Nucleic Acids Res. 1992;20:389-94 pubmed
    ..In contrast, no such retardation band was obtained between the FPG protein and double-stranded DNA containing an intact apurinic site or single-stranded DNA containing either an intact or a reduced apurinic site. ..
  45. Tie J, Uchigasaki S. DNA repair and STR PCR amplification from damaged DNA of human bloodstains. Mol Biol Rep. 2013;40:1505-10 pubmed publisher
  46. Pestryakov P, Zharkov D, Grin I, Fomina E, Kim E, Hamon L, et al. Effect of the multifunctional proteins RPA, YB-1, and XPC repair factor on AP site cleavage by DNA glycosylase NEIL1. J Mol Recognit. 2012;25:224-33 pubmed publisher
    ..Xeroderma pigmentosum complementation group C protein (XPC), a key protein of another DNA repair pathway, was shown to interact directly with AP sites but had no effect on AP site cleavage by NEIL1. ..
  47. Vijayavel K, Downs C, Ostrander G, Richmond R. Oxidative DNA damage induced by iron chloride in the larvae of the lace coral Pocillopora damicornis. Comp Biochem Physiol C Toxicol Pharmacol. 2012;155:275-80 pubmed publisher
    ..002, 0.003, 0.002, 0.002, 0.005 and 0.007) differences when compared to the control group. The research results indicated that iron chloride in concentrations at the 100 ppm level caused oxidative stress in the P. damicornis larvae. ..
  48. Mol C, Hosfield D, Tainer J. Abasic site recognition by two apurinic/apyrimidinic endonuclease families in DNA base excision repair: the 3' ends justify the means. Mutat Res. 2000;460:211-29 pubmed
    ..Each enzyme-DNA complex exhibits distinctly different DNA conformations, which may impact upon the biological functions of each enzyme within BER signal-transduction pathways. ..
  49. David Cordonnier M, Boiteux S, O NEILL P. Excision of 8-oxoguanine within clustered damage by the yeast OGG1 protein. Nucleic Acids Res. 2001;29:1107-13 pubmed
    ..Therefore, this large inhibitory effect of an AP site or a SSB may minimise the probability of formation of a double-strand break in the processing of 8-oxoG within clustered damages. ..
  50. Fujimoto H, Pinak M, Nemoto T, O Neill P, Kume E, Saito K, et al. Molecular dynamics simulation of clustered DNA damage sites containing 8-oxoguanine and abasic site. J Comput Chem. 2005;26:788-98 pubmed
    ..From these results it is suggested that these changes would make it difficult for the repair enzyme to bind to the lesions within the clustered damage site and thereby result in a reduction of its repair capacity. ..
  51. David Cordonnier M, Laval J, O NEILL P. Recognition and kinetics for excision of a base lesion within clustered DNA damage by the Escherichia coli proteins Fpg and Nth. Biochemistry. 2001;40:5738-46 pubmed
  52. Rabow L, Venkataraman R, Kow Y. Mechanism of action of Escherichia coli formamidopyrimidine N-glycosylase: role of K155 in substrate binding and product release. Prog Nucleic Acid Res Mol Biol. 2001;68:223-34 pubmed
    ..This is consistent with the idea that K155A dissociates prematurely from the covalent complex, leading to a higher turnover number observed for K155A for DNA substrate containing an AP site. ..
  53. Nakamura J, Purvis E, Swenberg J. Micromolar concentrations of hydrogen peroxide induce oxidative DNA lesions more efficiently than millimolar concentrations in mammalian cells. Nucleic Acids Res. 2003;31:1790-5 pubmed
    ..These results suggest that ADLs induced by submillimolar levels of H2O2 may be due to a Fenton-type reaction between H2O2 and intracellular iron ions in mammalian cells. ..