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Gene Review

xthA  -  exonuclease III

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK1747, JW1738, xth
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Disease relevance of xthA


High impact information on xthA

  • Structure and function of the multifunctional DNA-repair enzyme exonuclease III [6].
  • Nicking of the pBQ-dC adduct also leads to the same "dangling base" cleavage when two Escherichia coli enzymes, exonuclease III and endonuclease IV, are used [7].
  • Exonuclease III recognizes urea residues in oxidized DNA [8].
  • The efficient expression of any DNA insert would require that the entire coding sequence be contiguous and that its termini be randomized by treatment with exonuclease III and nuclease S1 to vary the distance between the translational initiation codon and the synthetic ribosome binding site [9].
  • The Saccharomyces cerevisiae ETH1 gene, an inducible homolog of exonuclease III that provides resistance to DNA-damaging agents and limits spontaneous mutagenesis [10].

Chemical compound and disease context of xthA


Biological context of xthA

  • One class of mutants named katE was localized between pfkB and xthA at 37.8 min on the E. coli genome [16].
  • Linear plasmid multimers also accumulated in a recBC xthA triple mutant, but not an isogenic xth A mutant or an isogenic recBC mutant [17].
  • Premutational lesions undergo mutation frequency decline (MFD), which is subject to delay in the xthA mutant, pointing to some role of AP endonuclease in MFD, and further supporting involvement of AP sites in BU-induced mutagenesis [18].
  • To further investigate the roles of these AP endonucleases in DNA repair, we evaluated the sensitivity and mutagenesis of xthA and nfo strains after UVB and compared with UVC light [19].
  • Since nitroxides protected xthA cells from DNA scission caused by H2O2, it was anticipated that they would provide even greater protection for recA DNA repair-deficient cells of E. coli, which are more sensitive to H2O2-induced oxidative stress [20].

Anatomical context of xthA

  • Sedimentation analysis of cellular DNA after hydrogen peroxide treatment showed that reformation was absent in xthA, polA, and polC(Ts) strains but normal in a recA cell line [21].
  • These synthetic oligodeoxynucleotides are cleaved on the 5' side of the abasic site by endonuclease IV and by exonuclease III; they serve also as templates for avian myeloblastosis virus reverse transcriptase, Escherichia coli DNA polymerase I (Klenow fragment), and calf thymus DNA polymerase-alpha [22].
  • DNA-protein complex prepared from a host range mutant with a mutation mapping in the left 4% of the genome was digested with exonuclease III, hybridized to a wild type restriction fragment comprising the left 8% of the genome, and transfected into HeLa cells [23].
  • In order to study the preference of incorporation of the diastereoisomers of DHdTTP into DNA, salmon testes DNA, activated by exonuclease III, was used as a template for DNA polymerase I Klenow fragment in the presence of [3H]DHdTTP (S and R mixture) and normal nucleotides [24].
  • To study the effects of changing mtDNA repair capacity on overall cell survival following oxidative stress, we expressed a bacterial repair enzyme, Exonuclease III (ExoIII) containing the mitochondrial targeting signal of manganese superoxide dismutase, in a human malignant breast epithelial cell line, MDA-MB-231 [25].

Associations of xthA with chemical compounds


Regulatory relationships of xthA


Other interactions of xthA

  • Measurement of repair synthesis after hydrogen peroxide treatment demonstrated normal levels for recA mutants, a small amount for xthA mutants, and none for polA mutants [21].
  • For comparison, mutations in the xthA and recA genes of the same strains increased the sensitivity of the mutants to hydrogen peroxide by seven- and fivefold, respectively, showing that catalase was the primary defense against hydrogen peroxide [16].
  • Mutants defective in the recA, uvrA and xthA genes are more sensitive to heat than the wild-type [29].
  • A triple mutant strain (nth nfo xthA) exhibited the greatest sensitivity to near-UV-mediated lethality [30].
  • This suggests that thermotolerance is an inducible response capable of protecting cells from the lethal effects of heat, independently of recA, uvrA and xthA [29].

Analytical, diagnostic and therapeutic context of xthA

  • The essential ligation products were resistant to treatment with exonuclease III, indicating that they were closed circular molecules [31].
  • By means of mobility-shift assays and Exonuclease III mapping we have determined a 14 bp sequence (named CDF2 binding site) located in front of the 16S rRNA initiation start site which is protected by a spinach chloroplast extract [32].
  • Purification, crystallization and space group determination of DNA repair enzyme exonuclease III from E. coli [33].
  • The circular DNA is resistant to the action of Escherichia coli exonuclease III and T7 exonuclease, but becomes sensitive to these nucleases after treatment with Pronase showing the presence of a protein that binds non-covalently to the ends of the DNA to circularize it as well as protect it from digestion with exonucleases [34].
  • It involves (a) the synchronous digestion of the DNA from the 3' ends with exonuclease III, followed by (b) repair synthesis with labeled nucleotides and DNA polymerase, and (c) sequence analysis of the repaired DNA [35].


  1. Genetic mapping of xthA, the structural gene for exonuclease III in Escherichia coli K-12. White, B.J., Hochhauser, S.J., Cintron, N.M., Weiss, B. J. Bacteriol. (1976) [Pubmed]
  2. A mutant endonuclease IV of Escherichia coli loses the ability to repair lethal DNA damage induced by hydrogen peroxide but not that induced by methyl methanesulfonate. Izumi, T., Ishizaki, K., Ikenaga, M., Yonei, S. J. Bacteriol. (1992) [Pubmed]
  3. W-reactivation and W-mutagenesis of gamma-irradiated phage lambda. Bresler, S.E., Kalinin, V.L., Shelegedin, V.N. Mutat. Res. (1978) [Pubmed]
  4. Alpha-deoxyadenosine, a major anoxic radiolysis product of adenine in DNA, is a substrate for Escherichia coli endonuclease IV. Ide, H., Tedzuka, K., Shimzu, H., Kimura, Y., Purmal, A.A., Wallace, S.S., Kow, Y.W. Biochemistry (1994) [Pubmed]
  5. Development of T7 phage and T7 phage containing apurinic sites in an exonuclease III, endonuclease IV double mutant of Escherichia coli. Sanchez, G., Mamet-Bratley, M.D. Biochem. Cell Biol. (1992) [Pubmed]
  6. Structure and function of the multifunctional DNA-repair enzyme exonuclease III. Mol, C.D., Kuo, C.F., Thayer, M.M., Cunningham, R.P., Tainer, J.A. Nature (1995) [Pubmed]
  7. An unusual mechanism for the major human apurinic/apyrimidinic (AP) endonuclease involving 5' cleavage of DNA containing a benzene-derived exocyclic adduct in the absence of an AP site. Hang, B., Chenna, A., Fraenkel-Conrat, H., Singer, B. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. Exonuclease III recognizes urea residues in oxidized DNA. Kow, Y.W., Wallace, S.S. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  9. Construction of a general vector for efficient expression of mammalian proteins in bacteria: use of a synthetic ribosome binding site. Jay, G., Khoury, G., Seth, A.K., Jay, E. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  10. 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]
  11. Role of exonuclease III and endonuclease IV in repair of pyrimidine dimers initiated by bacteriophage T4 pyrimidine dimer-DNA glycosylase. Saporito, S.M., Gedenk, M., Cunningham, R.P. J. Bacteriol. (1989) [Pubmed]
  12. Repair of DNA lesions induced by hydrogen peroxide in the presence of iron chelators in Escherichia coli: participation of endonuclease IV and Fpg. Galhardo, R.S., Almeida, C.E., Leitão, A.C., Cabral-Neto, J.B. J. Bacteriol. (2000) [Pubmed]
  13. Nitroxides block DNA scission and protect cells from oxidative damage. Samuni, A., Godinger, D., Aronovitch, J., Russo, A., Mitchell, J.B. Biochemistry (1991) [Pubmed]
  14. Escherichia coli xthA mutant is not hypersensitive to ascorbic acid/copper treatment--an H2O2 generating reaction. Van Sluys, M.A., Alcantara-Gomes, R., Menck, C.F. Mutat. Res. (1986) [Pubmed]
  15. In situ detection of AP sites and DNA strand breaks bearing 3'-phosphate termini in ischemic mouse brain. Huang, D., Shenoy, A., Cui, J., Huang, W., Liu, P.K. FASEB J. (2000) [Pubmed]
  16. Isolation of catalase-deficient Escherichia coli mutants and genetic mapping of katE, a locus that affects catalase activity. Loewen, P.C. J. Bacteriol. (1984) [Pubmed]
  17. Linear multimer formation of plasmid DNA in Escherichia coli hopE (recD) mutants. Niki, H., Ogura, T., Hiraga, S. Mol. Gen. Genet. (1990) [Pubmed]
  18. Involvement of DNA lesions and SOS functions in 5-bromouracil-induced mutagenesis. Pietrzykowska, I., Krych, M., Shugar, D. Mutat. Res. (1985) [Pubmed]
  19. Endonuclease IV and Exonuclease III are involved in the repair and mutagenesis of DNA lesions induced by UVB in Escherichia coli. Souza, L.L., Eduardo, I.R., Pádula, M., Leitão, A.C. Mutagenesis (2006) [Pubmed]
  20. Opposing effects of nitroxide free radicals in Escherichia coli mutants deficient in DNA repair. Wang, G., Godinger, D., Aronovitch, J., Samuni, A. Biochim. Biophys. Acta (1996) [Pubmed]
  21. Multiple pathways for repair of hydrogen peroxide-induced DNA damage in Escherichia coli. Hagensee, M.E., Moses, R.E. J. Bacteriol. (1989) [Pubmed]
  22. Oligodeoxynucleotides containing synthetic abasic sites. Model substrates for DNA polymerases and apurinic/apyrimidinic endonucleases. Takeshita, M., Chang, C.N., Johnson, F., Will, S., Grollman, A.P. J. Biol. Chem. (1987) [Pubmed]
  23. Adenovirus terminal protein protects single stranded DNA from digestion by a cellular exonuclease. Dunsworth-Browne, M., Schell, R.E., Berk, A.J. Nucleic Acids Res. (1980) [Pubmed]
  24. Synthesis of dihydrothymidine and thymidine glycol 5'-triphosphates and their ability to serve as substrates for Escherichia coli DNA polymerase I. Ide, H., Melamede, R.J., Wallace, S.S. Biochemistry (1987) [Pubmed]
  25. The expression of Exonuclease III from E. coli in mitochondria of breast cancer cells diminishes mitochondrial DNA repair capacity and cell survival after oxidative stress. Shokolenko, I.N., Alexeyev, M.F., Robertson, F.M., LeDoux, S.P., Wilson, G.L. DNA Repair (Amst.) (2003) [Pubmed]
  26. The cadmium-stress stimulon of Escherichia coli K-12. Ferianc, P., Farewell, A., Nyström, T. Microbiology (Reading, Engl.) (1998) [Pubmed]
  27. Cleavage of single- and double-stranded DNAs containing an abasic residue by Escherichia coli exonuclease III (AP endonuclease VI). Shida, T., Noda, M., Sekiguchi, J. Nucleic Acids Res. (1996) [Pubmed]
  28. Endonuclease IV (nfo) mutant of Escherichia coli. Cunningham, R.P., Saporito, S.M., Spitzer, S.G., Weiss, B. J. Bacteriol. (1986) [Pubmed]
  29. Requirement of the Escherichia coli dnaK gene for thermotolerance and protection against H2O2. Delaney, J.M. J. Gen. Microbiol. (1990) [Pubmed]
  30. Endonuclease III and endonuclease IV protect Escherichia coli from the lethal and mutagenic effects of near-UV irradiation. Serafini, D.M., Schellhorn, H.E. Can. J. Microbiol. (1999) [Pubmed]
  31. Site-specific insertion of gene cassettes into integrons. Collis, C.M., Grammaticopoulos, G., Briton, J., Stokes, H.W., Hall, R.M. Mol. Microbiol. (1993) [Pubmed]
  32. Characterization of a protein binding sequence in the promoter region of the 16S rRNA gene of the spinach chloroplast genome. Baeza, L., Bertrand, A., Mache, R., Lerbs-Mache, S. Nucleic Acids Res. (1991) [Pubmed]
  33. Purification, crystallization and space group determination of DNA repair enzyme exonuclease III from E. coli. Kuo, C.F., McRee, D.E., Cunningham, R.P., Tainer, J.A. J. Mol. Biol. (1993) [Pubmed]
  34. Infecting bacteriophage mu DNA forms a circular DNA-protein complex. Harshey, R.M., Bukhari, A.I. J. Mol. Biol. (1983) [Pubmed]
  35. Synchronous digestion of SV40 DNA by exonuclease III. Wu, R., Ruben, G., Siegel, B., Jay, E., Spielman, P., Tu, C.P. Biochemistry (1976) [Pubmed]
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