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Gene Review

APN1  -  DNA-(apurinic or apyrimidinic site) lyase...

Saccharomyces cerevisiae S288c

Synonyms: AP endonuclease 1, Apurinic-apyrimidinic endonuclease 1, DNA-(apurinic or apyrimidinic site) lyase 1, YKL114C, YKL513
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Disease relevance of APN1


High impact information on APN1

  • Human HAP1 (REF1) encodes the major AP endonuclease which, in addition to its role in DNA repair, functions as a redox regulatory protein [4].
  • In fact, apn1 apn2 rad1 triple mutants can form microcolonies of approximately 300 cells [5].
  • Other results presented here show that AP endonuclease-deficient Escherichia coli exhibit a mutator phenotype consistent with the A-rule [6].
  • With the yeast SUP4-o gene as a mutational target, we found that a deficiency in the major yeast AP endonuclease, Apn1, provoked mainly single base-pair substitution; the rate of transposon Ty insertion was also enhanced [6].
  • In the absence of APN1, the overexpression of MAG increased spontaneous mutation, and the underexpression of MAG decreased spontaneous mutation [7].

Chemical compound and disease context of APN1

  • Using uracil-containing DNA as a model substrate, we demonstrate that yeast BER requires Apn1 protein, an Escherichia coli endonuclease IV homolog [8].

Biological context of APN1


Anatomical context of APN1

  • A549 cells, an alveolar epithelial cell line, were transduced by MIEG3 retroviral vector encoding both enhanced green fluorescent protein (EGFP) and APN1 [2].
  • We have investigated here the effect of pure APN1 protein on BER performed by mouse embryonic fibroblast extracts [11].
  • Here we demonstrate for the first time that yeast Apn1p is also localized to the mitochondria [12].
  • We found that Pir1p, initially isolated as a cell wall constituent of unknown function, interacts with the C-terminal end of Apn1p, which bears a bipartite nuclear localization signal [12].

Associations of APN1 with chemical compounds

  • Double-mutant strains (apn1 eth1) were approximately 15-fold more sensitive to MMS and approximately 2- to 3-fold more sensitive to hydrogen peroxide and phleomycin D1 than were apn1 strains [1].
  • Elimination of ETH1 in apn1 strains also increased spontaneous mutation rates 9- or 31-fold compared to the wild type as determined by reversion to adenine or lysine prototrophy, respectively [1].
  • We have found that yeast cells simultaneously lacking Ntg1p, Ntg2p, and Apn1p are hyperrecombinogenic (hyper-rec) and exhibit a mutator phenotype but are not sensitive to the oxidizing agents H2O2 and menadione [9].
  • This species difference was due to the absence of delta-lyase activity in S. cerevisiae, since expression of bacterial Fpg conferred Tpp1-dependent resistance to methylmethane sulfonate in yeast lacking the abasic endonucleases Apn1 and Apn2 [13].
  • Deleting uracil glycosylase suppressed both tpp1 apn1 rad1 and apn1 apn2 rad1 growth defects by reducing the abasic site burden [10].

Physical interactions of APN1

  • We conclude that Pir1p interacts with Apn1p, at the level of either the cytoplasm or nucleus, and facilitates Apn1p transport into the mitochondria to repair damaged DNA [12].

Regulatory relationships of APN1

  • Mutants affecting the Chk1-Pds1 metaphase-anaphase checkpoint only suppressed tpp1 apn1 rad1 slow growth [10].
  • Consistent with these biochemical observations, genetic studies indicate the involvement of APN2 in the repair of H(2)O(2)-induced DNA damage in a pathway alternate to APN1, and the Ala59 mutation inactivates this function of Apn2 [14].

Other interactions of APN1

  • However, mag1 and apn1 mutants that are also defective in nucleotide excision repair are extremely sensitive to MMS-induced killing and the effects are synergistic [15].
  • The second assay uses the apn1 apn2 rad14 triple mutant, which is viable but exhibits a spontaneous mutator phenotype [16].
  • Thus, the recombination repair defects of rad1 and rad10 may confer an additional synergistic effect when combined with the apn1 mutation [15].
  • Deletion of TPP1 in an apn1 apn2 mutant background dramatically increased the sensitivity of the double mutant to DNA damage caused by H2O2 and bleomycin but not to damage caused by methyl methanesulfonate [17].
  • We have used the previously described technique of random-breakage mapping to locate the two yeast genes APN1 and YUH1 [18].

Analytical, diagnostic and therapeutic context of APN1


  1. The Saccharomyces cerevisiae ETH1 gene, an inducible homolog of exonuclease III that provides resistance to DNA-damaging agents and limits spontaneous mutagenesis. Bennett, R.A. Mol. Cell. Biol. (1999) [Pubmed]
  2. Expression of yeast apurinic/apyrimidinic endonuclease (APN1) protects lung epithelial cells from bleomycin toxicity. He, Y.H., Wu, M., Kobune, M., Xu, Y., Kelley, M.R., Martin, W.J. Am. J. Respir. Cell Mol. Biol. (2001) [Pubmed]
  3. Genotoxin resistance properties of transgenic tobacco plants expressing bacteriophage T4 DenV and Saccharomyces cerevisiae Apn1 proteins. Lapointe, G., Winchcombe-Forhan, C., Evans, D.H. Biochem. Cell Biol. (1997) [Pubmed]
  4. Identification of APN2, the Saccharomyces cerevisiae homolog of the major human AP endonuclease HAP1, and its role in the repair of abasic sites. Johnson, R.E., Torres-Ramos, C.A., Izumi, T., Mitra, S., Prakash, S., Prakash, L. Genes Dev. (1998) [Pubmed]
  5. Endogenous DNA abasic sites cause cell death in the absence of Apn1, Apn2 and Rad1/Rad10 in Saccharomyces cerevisiae. Guillet, M., Boiteux, S. EMBO J. (2002) [Pubmed]
  6. Specificity of the mutator caused by deletion of the yeast structural gene (APN1) for the major apurinic endonuclease. Kunz, B.A., Henson, E.S., Roche, H., Ramotar, D., Nunoshiba, T., Demple, B. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  7. In vivo evidence for endogenous DNA alkylation damage as a source of spontaneous mutation in eukaryotic cells. Xiao, W., Samson, L. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  8. Molecular mechanism of base excision repair of uracil-containing DNA in yeast cell-free extracts. Wang, Z., Wu, X., Friedberg, E.C. J. Biol. Chem. (1997) [Pubmed]
  9. Overlapping specificities of base excision repair, nucleotide excision repair, recombination, and translesion synthesis pathways for DNA base damage in Saccharomyces cerevisiae. Swanson, R.L., Morey, N.J., Doetsch, P.W., Jinks-Robertson, S. Mol. Cell. Biol. (1999) [Pubmed]
  10. Abrogation of the Chk1-Pds1 checkpoint leads to tolerance of persistent single-strand breaks in Saccharomyces cerevisiae. Karumbati, A.S., Wilson, T.E. Genetics (2005) [Pubmed]
  11. Effect of S. cerevisiae APN1 protein on mammalian DNA base excision repair. Bogliolo, M., Cappelli, E., D'Osualdo, A., Rossi, O., Barbieri, O., Kelley, M.R., Frosina, G. Anticancer Res. (2003) [Pubmed]
  12. Pir1p mediates translocation of the yeast Apn1p endonuclease into the mitochondria to maintain genomic stability. Vongsamphanh, R., Fortier, P.K., Ramotar, D. Mol. Cell. Biol. (2001) [Pubmed]
  13. The role of yeast DNA 3'-phosphatase Tpp1 and rad1/Rad10 endonuclease in processing spontaneous and induced base lesions. Karumbati, A.S., Deshpande, R.A., Jilani, A., Vance, J.R., Ramotar, D., Wilson, T.E. J. Biol. Chem. (2003) [Pubmed]
  14. 3'-phosphodiesterase and 3'-->5' exonuclease activities of yeast Apn2 protein and requirement of these activities for repair of oxidative DNA damage. Unk, I., Haracska, L., Prakash, S., Prakash, L. Mol. Cell. Biol. (2001) [Pubmed]
  15. Synergism between yeast nucleotide and base excision repair pathways in the protection against DNA methylation damage. Xiao, W., Chow, B.L. Curr. Genet. (1998) [Pubmed]
  16. Use of yeast for detection of endogenous abasic lesions, their source, and their repair. Boiteux, S., Guillet, M. Meth. Enzymol. (2006) [Pubmed]
  17. Repair of DNA strand breaks by the overlapping functions of lesion-specific and non-lesion-specific DNA 3' phosphatases. Vance, J.R., Wilson, T.E. Mol. Cell. Biol. (2001) [Pubmed]
  18. The use of random-breakage mapping to locate the genes APN1 and YUH1 in the Saccharomyces genome, and to determine gene order near the left end of chromosome XI. Game, J., Bell, M., Ramotar, D., Miller, H. Yeast (1994) [Pubmed]
  19. Rapid isolation of any known genes from whole cells of yeast by PCR. Ramotar, D. Mol. Cell. Biochem. (1995) [Pubmed]
  20. Intracellular localization of the Apn1 DNA repair enzyme of Saccharomyces cerevisiae. Nuclear transport signals and biological role. Ramotar, D., Kim, C., Lillis, R., Demple, B. J. Biol. Chem. (1993) [Pubmed]
  21. Yeast oligonucleotide transformation: its mechanism and application to analysis of mutations induced by defined DNA lesions. Negishi, K., Hata, Y., Sanda, K., Hayatsu, H. Nucleic Acids Symp. Ser. (1997) [Pubmed]
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