Genomes and Genes
Gene Symbol: nth
Description: DNA glycosylase and apyrimidinic (AP) lyase (endonuclease III)
Alias: ECK1629, JW1625
Species: Escherichia coli str. K-12 substr. MG1655
- Cunningham R, Asahara H, Bank J, Scholes C, Salerno J, Surerus K, et al. Endonuclease III is an iron-sulfur protein. Biochemistry. 1989;28:4450-5 pubmed..94 type EPR signal characteristic of a [4Fe-4S]1+ cluster. These studies show that endonuclease III is unique in being both a DNA repair enzyme and an iron-sulfur protein. The function of the 4Fe-4S cluster remains to be established. ..
- Kroeger K, Hashimoto M, Kow Y, Greenberg M. Cross-linking of 2-deoxyribonolactone and its beta-elimination product by base excision repair enzymes. Biochemistry. 2003;42:2449-55 pubmed
- Matsumoto N, Hayashi R, Himoto M, Kuraoka I, Morita S, Hagiwara F, et al. Fluorescence detection of the endonuclease III reaction using modified oligonucleotides. Nucleic Acids Symp Ser (Oxf). 2009;:213-4 pubmed publisher..The substrate specificity was shown using Escherichia coli and human enzymes. ..
- Tan G, Lu J, Bitoun J, Huang H, Ding H. IscA/SufA paralogues are required for the [4Fe-4S] cluster assembly in enzymes of multiple physiological pathways in Escherichia coli under aerobic growth conditions. Biochem J. 2009;420:463-72 pubmed publisher..coli under aerobic conditions. ..
- Kow Y, Wallace S. Mechanism of action of Escherichia coli endonuclease III. Biochemistry. 1987;26:8200-6 pubmed
- Jurado J, Saparbaev M, Matray T, Greenberg M, Laval J. The ring fragmentation product of thymidine C5-hydrate when present in DNA is repaired by the Escherichia coli Fpg and Nth proteins. Biochemistry. 1998;37:7757-63 pubmed..alphaRT is a substrate for two purified enzymes from Escherichia coli involved in the repair of oxidized bases: the Nth and the Fpg proteins. The Fpg protein removes the alphaRT lesion more efficiently than the Nth protein...
- Purmal A, Lampman G, Bond J, Hatahet Z, Wallace S. Enzymatic processing of uracil glycol, a major oxidative product of DNA cytosine. J Biol Chem. 1998;273:10026-35 pubmed..The steady state kinetic parameters indicated that Ug was a better substrate for endo III and formamidopyrimidine DNA glycosylase than Tg; for endonuclease VIII, however, Tg was a better substrate. ..
- Cunningham R, Weiss B. Endonuclease III (nth) mutants of Escherichia coli. Proc Natl Acad Sci U S A. 1985;82:474-8 pubmed..An insertion mutation was produced by cloning the kanamycin-resistance gene of Tn5 into the plasmid copy of the nth gene...
- Takao M, Oohata Y, Kitadokoro K, Kobayashi K, Iwai S, Yasui A, et al. Human Nei-like protein NEIL3 has AP lyase activity specific for single-stranded DNA and confers oxidative stress resistance in Escherichia coli mutant. Genes Cells. 2009;14:261-70 pubmed publisher..Surprisingly, NEIL3 partially rescues an E. coli nth nei mutant from hydrogen peroxide sensitivity...
- Boal A, Yavin E, Barton J. DNA repair glycosylases with a [4Fe-4S] cluster: a redox cofactor for DNA-mediated charge transport?. J Inorg Biochem. 2007;101:1913-21 pubmed
- Kuo C, McRee D, Fisher C, O Handley S, Cunningham R, Tainer J. Atomic structure of the DNA repair [4Fe-4S] enzyme endonuclease III. Science. 1992;258:434-40 pubmed..Overall, the structure reveals an unusual fold and a new biological function for [4Fe-4S] clusters and provides a structural basis for studying recognition of damaged DNA and the N-glycosylase and apurinic/apyrimidinic-lyase mechanisms. ..
- Thayer M, Ahern H, Xing D, Cunningham R, Tainer J. Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure. EMBO J. 1995;14:4108-20 pubmed..The identification of HhH and FCL sequence patterns in other DNA binding proteins suggests that these motifs may be a recurrent structural theme for DNA binding proteins. ..
- Breimer L, Lindahl T. Thymine lesions produced by ionizing radiation in double-stranded DNA. Biochemistry. 1985;24:4018-22 pubmed..Isolation and analysis of the DNA from gamma-irradiated human cells also revealed the formation of ring-saturated thymine derivatives, but 5-hydroxy-5-methylhydantoin was not found in this case. ..
- Weiss B, Cunningham R. Genetic mapping of nth, a gene affecting endonuclease III (thymine glycol-DNA glycosylase) in Escherichia coli K-12. J Bacteriol. 1985;162:607-10 pubmedThe nth gene of Escherichia coli affects the production of endonuclease III, a glycosylase-endonuclease that attacks DNA damaged by oxidizing agents or by ionizing radiation. An nth insertion mutant and a deletion mutant were studied...
- Sikora A, Mielecki D, Chojnacka A, Nieminuszczy J, Wrzesinski M, Grzesiuk E. Lethal and mutagenic properties of MMS-generated DNA lesions in Escherichia coli cells deficient in BER and AlkB-directed DNA repair. Mutagenesis. 2010;25:139-47 pubmed publisher..In the xth nth nfo strain additionally mutated in alkB gene, all these effects were extreme and led to 'error catastrophe', ..
- Boiteux S. Properties and biological functions of the NTH and FPG proteins of Escherichia coli: two DNA glycosylases that repair oxidative damage in DNA. J Photochem Photobiol B. 1993;19:87-96 pubmed..The first step in this DNA repair pathway is catalysed either by the NTH protein which excises oxidized pyrimidines or by the FPG protein which excises oxidized purines...
- Lomax M, Salje H, Cunniffe S, O Neill P. 8-OxoA inhibits the incision of an AP site by the DNA glycosylases Fpg, Nth and the AP endonuclease HAP1. Radiat Res. 2005;163:79-84 pubmed..The influence 8-oxoA has on the incision of the AP site by the E. coli glycosylases Fpg and Nth protein and the human AP endonuclease HAP1 was assessed...
- Katcher H, Wallace S. Characterization of the Escherichia coli X-ray endonuclease, endonuclease III. Biochemistry. 1983;22:4071-81 pubmed..The glycosylase activity is sensitive to N-ethylmaleimide while the AP endonuclease is not. ..
- Doi Y, Katafuchi A, Fujiwara Y, Hitomi K, Tainer J, Ide H, et al. Synthesis and characterization of oligonucleotides containing 2'-fluorinated thymidine glycol as inhibitors of the endonuclease III reaction. Nucleic Acids Res. 2006;34:1540-51 pubmed..The 5S isomer was found to form an enzyme-DNA complex, but the incision was inhibited probably by the fluorine-induced stabilization of the glycosidic bond. ..
- Saito Y, Uraki F, Nakajima S, Asaeda A, Ono K, Kubo K, et al. Characterization of endonuclease III (nth) and endonuclease VIII (nei) mutants of Escherichia coli K-12. J Bacteriol. 1997;179:3783-5 pubmedThe nth and nei genes of Escherichia coli affect the production of endonuclease III and endonuclease VIII, respectively, glycosylases/apurinic lyases that attack DNA damaged by oxidizing agents...
- D Ham C, Romieu A, Jaquinod M, Gasparutto D, Cadet J. Excision of 5,6-dihydroxy-5,6-dihydrothymine, 5,6-dihydrothymine, and 5-hydroxycytosine from defined sequence oligonucleotides by Escherichia coli endonuclease III and Fpg proteins: kinetic and mechanistic aspects. Biochemistry. 1999;38:3335-44 pubmed
- Banath J, Wallace S, Thompson J, Olive P. Radiation-induced DNA base damage detected in individual aerobic and hypoxic cells with endonuclease III and formamidopyrimidine-glycosylase. Radiat Res. 1999;151:550-8 pubmed..0, and (2) the presence of direct DNA strand breaks (>2000-4000 per cell) prevents accurate detection of base damage measured as enzyme-sensitive sites with the alkaline comet method. ..
- Wiederholt C, Patro J, Jiang Y, Haraguchi K, Greenberg M. Excision of formamidopyrimidine lesions by endonucleases III and VIII is not a major DNA repair pathway in Escherichia coli. Nucleic Acids Res. 2005;33:3331-8 pubmed..O. Blaisdell, Z. Hatahet and S. S. Wallace (1999) J. Bacteriol., 181, 6396-6402], these results also suggest that Endo III and Endo VIII do not protect E.coli against possible mutations attributable to formamidopyrimidine lesions. ..
- Privezentzev C, Saparbaev M, Sambandam A, Greenberg M, Laval J. AlkA protein is the third Escherichia coli DNA repair protein excising a ring fragmentation product of thymine. Biochemistry. 2000;39:14263-8 pubmed..It was shown that alphaRT is excised by Escherichia coli Fpg and Nth proteins. Here we report that when present in DNA, alphaRT is, in addition, a substrate for the E...
- Lhiaubet Vallet V, Sarabia Z, Hernandez D, Castell J, Miranda M. In vitro studies on DNA-photosensitization by different drug stereoisomers. Toxicol In Vitro. 2003;17:651-6 pubmed..In the case of carprofen the (S) isomer appears to be somewhat less active than its (R) enantiomer. However, due to the small differences found, the possible stereoselectivity has to be confirmed by future studies. ..
- Laval J. Role of DNA repair enzymes in the cellular resistance to oxidative stress. Pathol Biol (Paris). 1996;44:14-24 pubmed..Efficient DNA repair mechanisms remove these oxidized bases. In Escherichia coli cells, endonuclease III (NTH protein) and endonuclease VIII (NEI protein) excise many oxidized pyrimidines, whereas the FPG protein (..
- Mazumder A, Gerlt J, Absalon M, Stubbe J, Cunningham R, Withka J, et al. Stereochemical studies of the beta-elimination reactions at aldehydic abasic sites in DNA: endonuclease III from Escherichia coli, sodium hydroxide, and Lys-Trp-Lys. Biochemistry. 1991;30:1119-26 pubmed
- Robey Bond S, Benson M, Barrantes Reynolds R, Bond J, Wallace S. Probing the activity of NTHL1 orthologs by targeting conserved amino acid residues. DNA Repair (Amst). 2017;53:43-51 pubmed publisher..Finally, we present evidence that hNTHL1 Asp144, unlike the analogous EcoNth residue Asp44, may be involved in resolving the glycosylase transition state. ..
- David Cordonnier M, Laval J, O NEILL P. Clustered DNA damage, influence on damage excision by XRS5 nuclear extracts and Escherichia coli Nth and Fpg proteins. J Biol Chem. 2000;275:11865-73 pubmed..Escherichia coli Nth and Fpg and nuclear extracts from XRS5, a Chinese hamster ovary Ku-deficient cell line, have been used to study the ..
- Gifford C, Wallace S. The genes encoding endonuclease VIII and endonuclease III in Escherichia coli are transcribed as the terminal genes in operons. Nucleic Acids Res. 2000;28:762-9 pubmed..The genes encoding these proteins, nei and nth, are both co-transcribed as the terminal genes in operons...
- Aiub C, Mazzei J, Pinto L, Felzenszwalb I. Participation of BER and NER pathways in the repair of DNA lesions induced at low N-nitrosodiethylamine concentrations. Toxicol Lett. 2004;154:133-42 pubmed..through cell survival, in different single and double Escherichia coli DNA repair mutants (uvrA, uvrB, uvrC, fpg, nth, xthA, fpg/nth, uvrA/fpg, fpg/xthA, mutY, and fpg/mutY), using pre-incubation periods of 90 min...
- Warner H, Demple B, Deutsch W, Kane C, Linn S. Apurinic/apyrimidinic endonucleases in repair of pyrimidine dimers and other lesions in DNA. Proc Natl Acad Sci U S A. 1980;77:4602-6 pubmed..They also imply that the glycosylic bond is cleaved before the phosphodiester bond. ..
- Romano C, Sontz P, Barton J. Mutants of the base excision repair glycosylase, endonuclease III: DNA charge transport as a first step in lesion detection. Biochemistry. 2011;50:6133-45 pubmed publisher..These results demonstrate a link between the ability of the repair protein to carry out DNA CT and its ability to relocalize near lesions, thus pointing to DNA CT as a key first step in the detection of base damage in the genome. ..
- Gates F, Linn S. Endonuclease from Escherichia coli that acts specifically upon duplex DNA damaged by ultraviolet light, osmium tetroxide, acid, or x-rays. J Biol Chem. 1977;252:2802-7 pubmed..The enzyme is possibly the same as E. coli endonuclease III described by Radman (Radman, M. (1976) J. Biol. Chem. 251, 1438-1445), but it is distinguishable from the other endodeoxyribonucleases described from that organism. ..
- Bailly V, Verly W. AP endonucleases and AP lyases. Nucleic Acids Res. 1989;17:3617-8 pubmed
- Breimer L, Lindahl T. A DNA glycosylase from Escherichia coli that releases free urea from a polydeoxyribonucleotide containing fragments of base residues. Nucleic Acids Res. 1980;8:6199-211 pubmed..Since fragmentation of pyrimidine residues is a major type of base lesion introduced in DNA by exposure to ionizing radiation, it seems likely this DNA glycosylase is active in repair of X-ray-induced lesions. ..
- Denver D, Swenson S, Lynch M. An evolutionary analysis of the helix-hairpin-helix superfamily of DNA repair glycosylases. Mol Biol Evol. 2003;20:1603-11 pubmed..glycosylase; MpgII: N-methylpurine glycosylase II; MutY/Mig: A/G-specific adenine glycosylase/mismatch glycosylase; Nth: endonuclease III; OggI: 8-oxoguanine glycosylase I; and OggII: 8-oxoguanine glycosylase II) are identified through ..
- Kim J, Linn S. The mechanisms of action of E. coli endonuclease III and T4 UV endonuclease (endonuclease V) at AP sites. Nucleic Acids Res. 1988;16:1135-41 pubmed..Whereas these enzymes use a lyase-like rather than a hydrolytic mechanism, they nonetheless catalyze phosphodiester bond cleavage. We suggest that the term endonuclease can be properly applied to them. ..
- Boal A, Genereux J, Sontz P, Gralnick J, Newman D, Barton J. Redox signaling between DNA repair proteins for efficient lesion detection. Proc Natl Acad Sci U S A. 2009;106:15237-42 pubmed publisher..These results illustrate how repair proteins might efficiently locate DNA lesions and point to a biological role for DNA-mediated CT within the cell. ..
- Speina E, Cieśla J, Graziewicz M, Laval J, Kazimierczuk Z, Tudek B. Inhibition of DNA repair glycosylases by base analogs and tryptophan pyrolysate, Trp-P-1. Acta Biochim Pol. 2005;52:167-78 pubmed..on the activity of base excision repair enzymes: Escherichia coli and human DNA glycosylases of oxidized (Fpg, Nth) and alkylated bases (TagA, AlkA, and ANPG), and for bacterial AP endonuclease (Xth protein)...
- 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. ..
- Cunningham R, Ahern H, Xing D, Thayer M, Tainer J. Structure and function of Escherichia coli endonuclease III. Ann N Y Acad Sci. 1994;726:215-22 pubmed
- Wagner J, Blount B, Weinfeld M. Excision of oxidative cytosine modifications from gamma-irradiated DNA by Escherichia coli endonuclease III and human whole-cell extracts. Anal Biochem. 1996;233:76-86 pubmed..In identical samples, the amount of product 2 was reduced by 45.0 +/- 2.6% (225 from 500 fmol per microgram of DNA) and that of product 4 by 7.0 +/- 3.1% (42 from 600 fmol per microgram of DNA) as measured by HPLC/EC analysis. ..
- Bailly V, Verly W. Escherichia coli endonuclease III is not an endonuclease but a beta-elimination catalyst. Biochem J. 1987;242:565-72 pubmed..The cleavage might be the result of a beta-elimination analogous to the one produced by an alkaline pH or Lys-Trp-Lys. Thus it would seem that E. coli 'endonuclease III' is, after all, not an endonuclease. ..
- Watanabe T, Blaisdell J, Wallace S, Bond J. Engineering functional changes in Escherichia coli endonuclease III based on phylogenetic and structural analyses. J Biol Chem. 2005;280:34378-84 pubmed..These three amino acids are highly conserved among Nth orthologs, although not among homologous glycosylases, such as MutY, that have different base specificities and no ..
- Chang P, Zhang Q, Takatori K, Tachibana A, Yonei S. Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli. Int J Radiat Biol. 2005;81:115-23 pubmed..An E. coli mutM nth nei triple mutant was less sensitive to the lethal effect of sparsely ionizing radiation (gamma-rays and X-rays) ..
- Boal A, Yavin E, Lukianova O, O Shea V, David S, Barton J. DNA-bound redox activity of DNA repair glycosylases containing [4Fe-4S] clusters. Biochemistry. 2005;44:8397-407 pubmed..This redox activation furthermore establishes a functional role for the ubiquitous [4Fe-4S] clusters in DNA repair enzymes that involves redox chemistry and provides a means to consider DNA-mediated signaling within the cell. ..
- Suzuki T, Yamamoto K, Harashima H, Kamiya H. Base excision repair enzyme endonuclease III suppresses mutagenesis caused by 8-hydroxy-dGTP. DNA Repair (Amst). 2008;7:88-94 pubmed..8-OH-dGTP) and 2-hydroxy-dATP were introduced into Escherichia coli strains deficient in endonucleases III (Nth) and VIII (Nei) and MutY, and mutations in the chromosomal rpoB gene were analyzed...
- Serafini D, Schellhorn H. Endonuclease III and endonuclease IV protect Escherichia coli from the lethal and mutagenic effects of near-UV irradiation. Can J Microbiol. 1999;45:632-7 pubmed..isogenic strains deficient in one or more of exonuclease III (xthA), endonuclease IV (nfo), and endonuclease III (nth) were exposed to increasing levels of far-UV and near-UV...
- Tano K, Iwamatsu Y, Yasuhira S, Utsumi H, Takimoto K. Increased base change mutations at G:C pairs in Escherichia coli deficient in endonuclease III and VIII. J Radiat Res. 2001;42:409-13 pubmed..G:C to T:A and to C:G transversions dominated in both mutants. These results suggest that endo III and endo VIII are involved in the repair of oxidative lesions of guanine. ..
- Janion C, Sikora A, Nowosielska A, Grzesiuk E. E. coli BW535, a triple mutant for the DNA repair genes xth, nth, and nfo, chronically induces the SOS response. Environ Mol Mutagen. 2003;41:237-42 pubmedA strong chronic induction of the SOS response system occurs in E. coli BW535, a strain defective in nth, nfo and xth genes, and hence severely deficient in the repair of abasic sites in DNA...
- Radman M. An endonuclease from Escherichia coli that introduces single polynucleotide chain scissions in ultraviolet-irradiated DNA. J Biol Chem. 1976;251:1438-45 pubmed..6; (g) it is a basic protein. The enzyme is tentatively named E. coli endonuclease III. The physiological function of the endonuclease has not yet been established. ..
- Speina E, Kierzek A, Tudek B. Chemical rearrangement and repair pathways of 1,N6-ethenoadenine. Mutat Res. 2003;531:205-17 pubmed..coli (Nth) and Saccharomyces cerevisiae (Ntg2)...
- Suzuki T, Yamamoto K, Harashima H, Kamiya H. Base excision repair system suppresses mutagenesis caused by 8-hydroxy-dGTP in Escherichia coli. Nucleic Acids Symp Ser (Oxf). 2007;:51-2 pubmed..pool, 8-hydroxy-dGTP (8-OH-dGTP) was introduced into Escherichia coli strains deficient in endonucleases III (Nth) and VIII (Nei), and MutY, and mutations in the chromosomal rpoB gene were analyzed...
- Gifford C, Blaisdell J, Wallace S. Multiprobe RNase protection assay analysis of mRNA levels for the Escherichia coli oxidative DNA glycosylase genes under conditions of oxidative stress. J Bacteriol. 2000;182:5416-24 pubmed..The genes fpg, mutY, nei, and nth encode Fpg, MutY, endonuclease VIII, and endonuclease III, respectively...
- Asahara H, Wistort P, Bank J, Bakerian R, Cunningham R. Purification and characterization of Escherichia coli endonuclease III from the cloned nth gene. Biochemistry. 1989;28:4444-9 pubmedThe gene which codes for endonuclease III of Escherichia coli has been sequenced. The nth gene was previously subcloned and defined as the gene which led to overproduction of endonuclease III when present on a multicopy plasmid and which ..
- Guliaev A, Singer B, Hang B. Chloroethylnitrosourea-derived ethano cytosine and adenine adducts are substrates for Escherichia coli glycosylases excising analogous etheno adducts. DNA Repair (Amst). 2004;3:1311-21 pubmed..However, also as shown by MD, the stacking interaction between the EC base and Phe 30 in the Mug active site is reduced as compared to the epsilonC base, which could account for the lower EC activity observed in this study. ..