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Gene Review

OGG1  -  8-oxoguanine DNA glycosylase

Homo sapiens

Synonyms: HMMH, HOGG1, MMH, MUTM, N-glycosylase/DNA lyase, ...
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Disease relevance of OGG1

  • One class utilizes an internal Lys residue as the active site nucleophile, and includes Escherichia coli Nth and both known mammalian DNA glycosylase/AP lyases, namely, OGG1 and NTH1 [1].
  • RESULTS: Polymorphism OGG1 S326C was associated with an increased risk of colorectal cancer [odds ratio (OR), 2.3; 95% confidence interval (95% CI), 1.1-5.0], the risk being higher in younger individuals [2].
  • They found increased lung cancer risk among subjects carrying the OGG1 Cys/Cys genotype (odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.01, 1.53), using 3,253 cases and 3,371 controls from seven studies; this is consistent with experimental evidence that this isoform exhibits decreased activity [3].
  • Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer [4].
  • In contrast, significant association was not observed for the GSTM1, CYP1A1, and OGG1 polymorphisms with lung adenocarcinoma risk, although several studies have shown their implication in the risk for squamous cell lung carcinoma [5].
  • A greater proportion of the hOGG1-over-expressing hepatoma cells experienced apoptosis [6].

Psychiatry related information on OGG1


High impact information on OGG1


Chemical compound and disease context of OGG1


Biological context of OGG1

  • We demonstrate that XPC-HR23B complex acts as cofactor in base excision repair of 8-OH-Gua, by stimulating the activity of its specific DNA glycosylase OGG1 [16].
  • Consistent with these results, deletion of both OGG1 encoding 8oxoG-DNA glycosylase and APN1 causes nearly 46-fold synergistic increase in the spontaneous mutation rate, and this enhanced mutagenesis is primarily due to G . C to T . A transversions [17].
  • The enhanced rate of repair of 8-oxoG in the genome by wild-type OGG1 but not the K338R/K341R mutant, ectopically expressed in oxidatively stressed OGG1-null mouse embryonic fibroblasts, suggests that acetylation increases OGG1 activity in vivo [18].
  • Based on these results, we propose a novel regulatory function of OGG1 acetylation in repair of its substrates in oxidatively stressed cells [18].
  • There is a great deal of interest in the up- or down-regulation of OGG1 expression after DNA damage [19].

Anatomical context of OGG1


Associations of OGG1 with chemical compounds

  • Western blotting and semiquantitative reverse transcription-PCR revealed that cadmium treatment caused a decrease in the expression level of human OGG1 (8-oxoguanine-DNA glycosylase-1; hOGG1) in human fibroblast GM00637 and HeLa S3 cells [23].
  • Transcription factors NF-YA regulate the induction of human OGG1 following DNA-alkylating agent methylmethane sulfonate (MMS) treatment [19].
  • This novel collaboration of two DNA glycosylases, which do not stably interact with each other, in stimulating 8-oxoguanine repair is possible because of higher AP site affinity and stronger AP lyase activity of NEIL1 relative to OGG1 [24].
  • Suppressive activities of OGG1 and MYH proteins against G:C to T:A mutations caused by 8-hydroxyguanine but not by benzo[a]pyrene diol epoxide in human cells in vivo [25].
  • Sodium dichromate at 25 microM and above gave a marked reduction of OGG1 mRNA expression which was not seen at 1 microM and below [26].

Physical interactions of OGG1


Enzymatic interactions of OGG1


Regulatory relationships of OGG1

  • The glycosylase activity of S326C OGG1 was not significantly stimulated by the presence of AP-endonuclease [27].
  • XRCC1 stimulates the formation of the hOGG1 Schiff-base DNA intermediate without interfering with the endonuclease activity of APE1, the second enzyme in the pathway [28].
  • Functional analysis showed that p53 significantly enhanced the sequential activities of hOGG1 and APE in excising the 8-oxoG nucleotide from DNA in vitro [31].
  • Using an 8-oxoguanine DNA glycosylase (OGG1)-specific siRNAs, we also found that MT-III expression resulted in the suppression of the gamma-radiation-induced 8-oxoG accumulation and mutation in the OGG1-depleted cells [32].
  • Furthermore, evidence is presented to support the hypothesis that wild type CSB regulates expression of OGG1 [33].

Other interactions of OGG1

  • Based on these observations, we further characterized expression and intracellular localization of 8-oxoG DNA glycosylase (hOGG1) and 2-OH-A/adenine DNA glycosylase (hMYH) in human cells [34].
  • Proteins related to DNA damage and repair, such as Ku, poly(ADP-ribosyl) polymerase, OGG1, and MSH2 were selectively up-regulated in malgun cells [35].
  • The mRNA levels of the nucleotide excision DNA repair gene ERCC1 and the base excision DNA repair gene OGG1 were quantified in 43 healthy volunteers in a dietary intervention trial as markers for the DNA repair capacity [36].
  • Stimulation of DNA glycosylase activity of OGG1 by NEIL1: functional collaboration between two human DNA glycosylases [24].
  • Using multifactor dimensionality reduction approach, the four-factor model, including smoking status, OGG1 S326C (rs1052133), APEX1 D148E (rs3136820), and ADPRT762 (rs1136410), had the best ability to predict bladder cancer risk with the highest cross-validation consistency (100%) and the lowest prediction error (37.02%; P < 0.001) [37].

Analytical, diagnostic and therapeutic context of OGG1


  1. 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]
  2. Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Moreno, V., Gemignani, F., Landi, S., Gioia-Patricola, L., Chabrier, A., Blanco, I., González, S., Guino, E., Capellà, G., Canzian, F. Clin. Cancer Res. (2006) [Pubmed]
  3. Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review. Hung, R.J., Hall, J., Brennan, P., Boffetta, P. Am. J. Epidemiol. (2005) [Pubmed]
  4. Polymorphisms in DNA repair genes and associations with cancer risk. Goode, E.L., Ulrich, C.M., Potter, J.D. Cancer Epidemiol. Biomarkers Prev. (2002) [Pubmed]
  5. Contribution of the NQO1 and GSTT1 polymorphisms to lung adenocarcinoma susceptibility. Sunaga, N., Kohno, T., Yanagitani, N., Sugimura, H., Kunitoh, H., Tamura, T., Takei, Y., Tsuchiya, S., Saito, R., Yokota, J. Cancer Epidemiol. Biomarkers Prev. (2002) [Pubmed]
  6. Targeting human 8-oxoguanine DNA glycosylase (hOGG1) to mitochondria enhances cisplatin cytotoxicity in hepatoma cells. Zhang, H., Mizumachi, T., Carcel-Trullols, J., Li, L., Naito, A., Spencer, H.J., Spring, P.M., Smoller, B.R., Watson, A.J., Margison, G.P., Higuchi, M., Fan, C.Y. Carcinogenesis (2007) [Pubmed]
  7. Expression of 8-oxoguanine DNA glycosylase is reduced and associated with neurofibrillary tangles in Alzheimer's disease brain. Iida, T., Furuta, A., Nishioka, K., Nakabeppu, Y., Iwaki, T. Acta Neuropathol. (2002) [Pubmed]
  8. Concomitant loss of mitochondria and the DNA repair protein hOGG1 in clear cell carcinoma of the kidney. Mukunyadzi, P., Huang, H., Liu, K., Fan, C.Y. Appl. Immunohistochem. Mol. Morphol. (2003) [Pubmed]
  9. Marathon running alters the DNA base excision repair in human skeletal muscle. Radák, Z., Apor, P., Pucsok, J., Berkes, I., Ogonovszky, H., Pavlik, G., Nakamoto, H., Goto, S. Life Sci. (2003) [Pubmed]
  10. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Bruner, S.D., Norman, D.P., Verdine, G.L. Nature (2000) [Pubmed]
  11. Augmented expression of a human gene for 8-oxoguanine DNA glycosylase (MutM) in B lymphocytes of the dark zone in lymph node germinal centers. Kuo, F.C., Sklar, J. J. Exp. Med. (1997) [Pubmed]
  12. 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]
  13. Radiation sensitivity depends on OGG1 activity status in human leukemia cell lines. Hyun, J.W., Cheon, G.J., Kim, H.S., Lee, Y.S., Choi, E.Y., Yoon, B.H., Kim, J.S., Chung, M.H. Free Radic. Biol. Med. (2002) [Pubmed]
  14. Lack of the DNA repair enzyme OGG1 sensitizes dopamine neurons to manganese toxicity during development. Cardozo-Pelaez, F., Cox, D.P., Bolin, C. Gene Expr. (2005) [Pubmed]
  15. Polymorphisms in estrogen bioactivation, detoxification and oxidative DNA base excision repair genes and prostate cancer risk. Nock, N.L., Cicek, M.S., Li, L., Liu, X., Rybicki, B.A., Moreira, A., Plummer, S.J., Casey, G., Witte, J.S. Carcinogenesis (2006) [Pubmed]
  16. New functions of XPC in the protection of human skin cells from oxidative damage. D'Errico, M., Parlanti, E., Teson, M., de Jesus, B.M., Degan, P., Calcagnile, A., Jaruga, P., Bjørås, M., Crescenzi, M., Pedrini, A.M., Egly, J.M., Zambruno, G., Stefanini, M., Dizdaroglu, M., Dogliotti, E. EMBO J. (2006) [Pubmed]
  17. The 3'->5' exonuclease of Apn1 provides an alternative pathway to repair 7,8-dihydro-8-oxodeoxyguanosine in Saccharomyces cerevisiae. Ishchenko, A.A., Yang, X., Ramotar, D., Saparbaev, M. Mol. Cell. Biol. (2005) [Pubmed]
  18. Acetylation of human 8-oxoguanine-DNA glycosylase by p300 and its role in 8-oxoguanine repair in vivo. Bhakat, K.K., Mokkapati, S.K., Boldogh, I., Hazra, T.K., Mitra, S. Mol. Cell. Biol. (2006) [Pubmed]
  19. Transcription factors NF-YA regulate the induction of human OGG1 following DNA-alkylating agent methylmethane sulfonate (MMS) treatment. Lee, M.R., Kim, S.H., Cho, H.J., Lee, K.Y., Moon, A.R., Jeong, H.G., Lee, J.S., Hyun, J.W., Chung, M.H., You, H.J. J. Biol. Chem. (2004) [Pubmed]
  20. DNA repair gene polymorphisms affect cytotoxicity in the National Cancer Institute Human Tumour Cell Line Screening Panel. Yarosh, D.B., Peña, A., Brown, D.A. Biomarkers (2005) [Pubmed]
  21. Possible involvement of XPA in repair of oxidative DNA damage deduced from analysis of damage, repair and genotype in a human population study. Dusinská, M., Dzupinková, Z., Wsólová, L., Harrington, V., Collins, A.R. Mutagenesis (2006) [Pubmed]
  22. The murine DNA glycosylase NEIL2 (mNEIL2) and human DNA polymerase beta bind microtubules in situ and in vitro. Conlon, K.A., Miller, H., Rosenquist, T.A., Zharkov, D.O., Berrios, M. DNA Repair (Amst.) (2005) [Pubmed]
  23. Cadmium down-regulates human OGG1 through suppression of Sp1 activity. Youn, C.K., Kim, S.H., Lee, d.o. .Y., Song, S.H., Chang, I.Y., Hyun, J.W., Chung, M.H., You, H.J. J. Biol. Chem. (2005) [Pubmed]
  24. Stimulation of DNA glycosylase activity of OGG1 by NEIL1: functional collaboration between two human DNA glycosylases. Mokkapati, S.K., Wiederhold, L., Hazra, T.K., Mitra, S. Biochemistry (2004) [Pubmed]
  25. Suppressive activities of OGG1 and MYH proteins against G:C to T:A mutations caused by 8-hydroxyguanine but not by benzo[a]pyrene diol epoxide in human cells in vivo. Yamane, A., Shinmura, K., Sunaga, N., Saitoh, T., Yamaguchi, S., Shinmura, Y., Yoshimura, K., Murakami, H., Nojima, Y., Kohno, T., Yokota, J. Carcinogenesis (2003) [Pubmed]
  26. Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells. Hodges, N.J., Chipman, J.K. Carcinogenesis (2002) [Pubmed]
  27. Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase. Hill, J.W., Evans, M.K. Nucleic Acids Res. (2006) [Pubmed]
  28. Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1. Marsin, S., Vidal, A.E., Sossou, M., Ménissier-de Murcia, J., Le Page, F., Boiteux, S., de Murcia, G., Radicella, J.P. J. Biol. Chem. (2003) [Pubmed]
  29. The effect of p53-RNAi and p53 knockout on human 8-oxoguanine DNA glycosylase (hOgg1) activity. Chatterjee, A., Mambo, E., Osada, M., Upadhyay, S., Sidransky, D. FASEB J. (2006) [Pubmed]
  30. Age-dependent modulation of DNA repair enzymes by covalent modification and subcellular distribution. Szczesny, B., Bhakat, K.K., Mitra, S., Boldogh, I. Mech. Ageing Dev. (2004) [Pubmed]
  31. Role of p53 in sensing oxidative DNA damage in response to reactive oxygen species-generating agents. Achanta, G., Huang, P. Cancer Res. (2004) [Pubmed]
  32. Metallothionein-III prevents gamma-ray-induced 8-oxoguanine accumulation in normal and hOGG1-depleted cells. Jeong, H.G., Youn, C.K., Cho, H.J., Kim, S.H., Kim, M.H., Kim, H.B., Chang, I.Y., Lee, Y.S., Chung, M.H., You, H.J. J. Biol. Chem. (2004) [Pubmed]
  33. Mitochondrial repair of 8-oxoguanine is deficient in Cockayne syndrome group B. Stevnsner, T., Nyaga, S., de Souza-Pinto, N.C., van der Horst, G.T., Gorgels, T.G., Hogue, B.A., Thorslund, T., Bohr, V.A. Oncogene (2002) [Pubmed]
  34. Regulation of intracellular localization of human MTH1, OGG1, and MYH proteins for repair of oxidative DNA damage. Nakabeppu, Y. Prog. Nucleic Acid Res. Mol. Biol. (2001) [Pubmed]
  35. Malgun (clear) cell change in Helicobacter pylori gastritis reflects epithelial genomic damage and repair. Jang, J., Lee, S., Jung, Y., Song, K., Fukumoto, M., Gould, V.E., Lee, I. Am. J. Pathol. (2003) [Pubmed]
  36. Inter-individual variation, seasonal variation and close correlation of OGG1 and ERCC1 mRNA levels in full blood from healthy volunteers. Vogel, U., Møller, P., Dragsted, L., Loft, S., Pedersen, A., Sandström, B. Carcinogenesis (2002) [Pubmed]
  37. High-order interactions among genetic variants in DNA base excision repair pathway genes and smoking in bladder cancer susceptibility. Huang, M., Dinney, C.P., Lin, X., Lin, J., Grossman, H.B., Wu, X. Cancer Epidemiol. Biomarkers Prev. (2007) [Pubmed]
  38. Oxidative DNA damage and human cancer: need for cohort studies. Loft, S., Møller, P. Antioxid. Redox Signal. (2006) [Pubmed]
  39. Induction of OGG1 gene expression by HIV-1 Tat. Imai, K., Nakata, K., Kawai, K., Hamano, T., Mei, N., Kasai, H., Okamoto, T. J. Biol. Chem. (2005) [Pubmed]
  40. Measurement of oxidative damage at individual gene levels by quantitative PCR using 8-hydroxyguanine glycosylase (OGG1). Choi, J., Kim, D.Y., Hyun, J.W., Yoon, S.H., Choi, E.M., Hahm, K.B., Rhee, K.H., Chung, M.H. Mutat. Res. (2003) [Pubmed]
  41. Structure and chromosome location of human OGG1. Ishida, T., Hippo, Y., Nakahori, Y., Matsushita, I., Kodama, T., Nishimura, S., Aburatani, H. Cytogenet. Cell Genet. (1999) [Pubmed]
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