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Gene Review

NTHL1  -  nth endonuclease III-like 1 (E. coli)

Homo sapiens

Synonyms: Bifunctional DNA N-glycoslyase/DNA-(apurinic or apyrimidinic site) lyase, DNA glycoslyase/AP lyase, Endonuclease III-like protein 1, NTH1, OCTS3, ...
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Disease relevance of NTHL1

  • Thymine glycol, a potentially lethal DNA lesion produced by reactive oxygen species, can be removed by DNA glycosylase, Escherichia coli Nth (endonuclease III), or its mammalian homologue NTH1 [1].
  • The activities of hOGG1 and hNTH1 were measured, using modified and 32P labelled oligonucleotides, in bronchial biopsy samples of smoking patients with non-small cell lung carcinoma [2].
  • However, it was observed that O2 toxicity did lead to a reduced endogenous expression of hNTH in A549 cells [3].
  • Cytoplasmic expression of NTH1 was detected in 35% of cases (28/81), which showed a significant correlation with lymph node metastasis (p=0.001), histological grade according to the Dukes' Classification (p=0.005), and disease-free survival (p=0.04) [4].
  • Expression of DNA repair protein: MYH, NTH1, and MTH1 in colorectal cancer [4].

High impact information on NTHL1


Chemical compound and disease context of NTHL1


Biological context of NTHL1


Anatomical context of NTHL1

  • Immunological studies showed that HeLa cells contain a single hNTH species of the predicted size, localized in both the nucleus and the cytoplasm [13].
  • By expressing the epitope-tagged proteins in COS-7 cells, we examined subcellular localizations of gene products of human DNA glycosylases: hOGG1, hMYH and hNTH1 [14].
  • We also show a correlation between severely defective incision of TG and 5OHC and reduced levels of NTH1 in PC-3 mitochondria [15].

Associations of NTHL1 with chemical compounds

  • Human endonuclease III (hNTH1), a DNA glycosylase with associated abasic lyase activity, repairs various mutagenic and toxic-oxidized DNA lesions, including thymine glycol [16].
  • In contrast, hNTH1 was not as inhibited by the AP:A site arising from release of Tg from Tg:A [8].
  • When Tg is opposite guanine (Tg:G), the two activities are of the same specific activity as the AP lyase activity of hNTH1 against Tg:A (Ocampo, M. T. A., Chaung, W., Marenstein, D. R., Chan, M. K., Altamirano, A., Basu, A. K., Boorstein, R. J., Cunningham, R. P., and Teebor, G. W. (2002) Mol. Cell. Biol. 22, 6111-6121) [8].
  • The specific activities of hNTH1 for cleavage of oligonucleotides containing 5-foU and thymine glycol were 0.011 and 0.045 nM/min/ng protein, respectively [17].
  • In human cells, the major DNA glycosylases for the excision of oxidative base damage are OGG1 and NTH1 that excise 8-oxoguanine and oxidative pyrimidines, respectively [18].

Physical interactions of NTHL1


Regulatory relationships of NTHL1

  • Studies with synchronised cells showed that the expression of hNTH1 is regulated during the cell cycle with increased transcription during early and mid S-phase [20].

Other interactions of NTHL1

  • These results suggest that NEIL1 is a back-up glycosylase for NTH1 with unique substrate specificity and tissue-specific expression [1].
  • In Escherichia coli, the DNA glycosylases Nei, Fpg, and Nth initiate BER of oxidative lesions; OGG1 and NTH1 proteins fulfill a similar function in mammalian cells [21].
  • These data were corroborated by Western blot analysis of APE1 and NTH1, suggesting that the BER enzymes are also not up-regulated at the post-transcriptional level after ionizing radiation exposure [22].
  • However, NEIL2 shows a unique preference for excising lesions from a DNA bubble, whereas NTH1 and OGG1 are only active with duplex DNA [23].
  • Lung cancer in smoking patients inversely alters the activity of hOGG1 and hNTH1 [2].


  1. A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue. Takao, M., Kanno, S., Kobayashi, K., Zhang, Q.M., Yonei, S., van der Horst, G.T., Yasui, A. J. Biol. Chem. (2002) [Pubmed]
  2. Lung cancer in smoking patients inversely alters the activity of hOGG1 and hNTH1. Radak, Z., Goto, S., Nakamoto, H., Udud, K., Papai, Z., Horvath, I. Cancer Lett. (2005) [Pubmed]
  3. Protection of pulmonary epithelial cells from oxidative stress by hMYH adenine glycosylase. Kremer, T.M., Rinne, M.L., Xu, Y., Chen, X.M., Kelley, M.R. Respir. Res. (2004) [Pubmed]
  4. Expression of DNA repair protein: MYH, NTH1, and MTH1 in colorectal cancer. Koketsu, S., Watanabe, T., Nagawa, H. Hepatogastroenterology (2004) [Pubmed]
  5. Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA. Hazra, T.K., Izumi, T., Boldogh, I., Imhoff, B., Kow, Y.W., Jaruga, P., Dizdaroglu, M., Mitra, S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. Cloning and characterization of a functional human homolog of Escherichia coli endonuclease III. Aspinwall, R., Rothwell, D.G., Roldan-Arjona, T., Anselmino, C., Ward, C.J., Cheadle, J.P., Sampson, J.R., Lindahl, T., Harris, P.C., Hickson, I.D. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  7. Differential specificity of human and Escherichia coli endonuclease III and VIII homologues for oxidative base lesions. Katafuchi, A., Nakano, T., Masaoka, A., Terato, H., Iwai, S., Hanaoka, F., Ide, H. J. Biol. Chem. (2004) [Pubmed]
  8. Substrate specificity of human endonuclease III (hNTH1). Effect of human APE1 on hNTH1 activity. Marenstein, D.R., Chan, M.K., Altamirano, A., Basu, A.K., Boorstein, R.J., Cunningham, R.P., Teebor, G.W. J. Biol. Chem. (2003) [Pubmed]
  9. Detection of oxidative clustered DNA lesions in X-irradiated mouse skin tissues and human MCF-7 breast cancer cells. Gollapalle, E., Wang, R., Adetolu, R., Tsao, D., Francisco, D., Sigounas, G., Georgakilas, A.G. Radiat. Res. (2007) [Pubmed]
  10. Escherichia coli Nth and human hNTH1 DNA glycosylases are involved in removal of 8-oxoguanine from 8-oxoguanine/guanine mispairs in DNA. Matsumoto, Y., Zhang, Q.M., Takao, M., Yasui, A., Yonei, S. Nucleic Acids Res. (2001) [Pubmed]
  11. Cloning and characterization of a mouse homologue (mNthl1) of Escherichia coli endonuclease III. Sarker, A.H., Ikeda, S., Nakano, H., Terato, H., Ide, H., Imai, K., Akiyama, K., Tsutsui, K., Bo, Z., Kubo, K., Yamamoto, K., Yasui, A., Yoshida, M.C., Seki, S. J. Mol. Biol. (1998) [Pubmed]
  12. Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes. Imai, K., Sarker, A.H., Akiyama, K., Ikeda, S., Yao, M., Tsutsui, K., Shohmori, T., Seki, S. Gene (1998) [Pubmed]
  13. Purification and characterization of human NTH1, a homolog of Escherichia coli endonuclease III. Direct identification of Lys-212 as the active nucleophilic residue. Ikeda, S., Biswas, T., Roy, R., Izumi, T., Boldogh, I., Kurosky, A., Sarker, A.H., Seki, S., Mitra, S. J. Biol. Chem. (1998) [Pubmed]
  14. Mitochondrial targeting of human DNA glycosylases for repair of oxidative DNA damage. Takao, M., Aburatani, H., Kobayashi, K., Yasui, A. Nucleic Acids Res. (1998) [Pubmed]
  15. Cellular repair of oxidatively induced DNA base lesions is defective in prostate cancer cell lines, PC-3 and DU-145. Trzeciak, A.R., Nyaga, S.G., Jaruga, P., Lohani, A., Dizdaroglu, M., Evans, M.K. Carcinogenesis (2004) [Pubmed]
  16. In vitro and in vivo dimerization of human endonuclease III stimulates its activity. Liu, X., Choudhury, S., Roy, R. J. Biol. Chem. (2003) [Pubmed]
  17. Identification of 5-formyluracil DNA glycosylase activity of human hNTH1 protein. Miyabe, I., Zhang, Q.M., Kino, K., Sugiyama, H., Takao, M., Yasui, A., Yonei, S. Nucleic Acids Res. (2002) [Pubmed]
  18. NEIL1 excises 3' end proximal oxidative DNA lesions resistant to cleavage by NTH1 and OGG1. Parsons, J.L., Zharkov, D.O., Dianov, G.L. Nucleic Acids Res. (2005) [Pubmed]
  19. Human NTH1 physically interacts with p53 and proliferating cell nuclear antigen. Oyama, M., Wakasugi, M., Hama, T., Hashidume, H., Iwakami, Y., Imai, R., Hoshino, S., Morioka, H., Ishigaki, Y., Nikaido, O., Matsunaga, T. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  20. Cell-cycle regulation, intracellular sorting and induced overexpression of the human NTH1 DNA glycosylase involved in removal of formamidopyrimidine residues from DNA. Luna, L., Bjørås, M., Hoff, E., Rognes, T., Seeberg, E. Mutat. Res. (2000) [Pubmed]
  21. The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death. Rosenquist, T.A., Zaika, E., Fernandes, A.S., Zharkov, D.O., Miller, H., Grollman, A.P. DNA Repair (Amst.) (2003) [Pubmed]
  22. Expression of the oxidative base excision repair enzymes is not induced in TK6 human lymphoblastoid cells after low doses of ionizing radiation. Inoue, M., Shen, G.P., Chaudhry, M.A., Galick, H., Blaisdell, J.O., Wallace, S.S. Radiat. Res. (2004) [Pubmed]
  23. Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2. Dou, H., Mitra, S., Hazra, T.K. J. Biol. Chem. (2003) [Pubmed]
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