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Gene Review

SMUG1  -  single-strand-selective monofunctional...

Homo sapiens

Synonyms: FDG, HMUDG, Single-strand selective monofunctional uracil DNA glycosylase, UNG3
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Disease relevance of SMUG1


Psychiatry related information on SMUG1

  • CONCLUSION: This investigation confirms that FDG PET is the best predictor of viable residual tumor in postchemotherapy seminoma residuals and should be used as a standard tool for clinical decision making in this patient group [6].
  • A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal controls and 395 patients with probable Alzheimer's disease (AD) that were studied in eight participating centers [7].
  • Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET [7].
  • Symptomatic Huntington's disease patients showed a marked reduction of FDG and RACLO uptake in the caudate nucleus and putamen and a significant increase of BCR [8].
  • Seven patients, presenting CSWS associated with neuropsychological deterioration (isolated aphasia, three cases; language disturbances with more widespread cognitive deterioration, three cases; isolated apraxia, one case) were studied using PET with [18F]fluorodeoxyglucose (FDG) [9].

High impact information on SMUG1

  • A corresponding catalytic mechanism could apply to the DNA glycosylases TDG and SMUG1, which belong to the same structural superfamily as UDG [10].
  • Our results may explain why SMUG1 cannot compensate the UNG2 deficiency in human B cells, and are fully consistent with the DNA deamination model that requires active nuclear UNG2 [11].
  • In B cell lines from hyper-IgM patients carrying UNG mutations, the single-strand-specific uracil-DNA glycosylase, SMUG1, cannot complement this function [11].
  • Attenuation-corrected transaxial and coronal images were visually evaluated by two nuclear medicine physicians (blinded to the patient's medical history) for foci of increased F-18 FDG uptake in the axilla region [3].
  • In lean individuals, insulin stimulated a 10-fold increase of 2-deoxy-2[18F]fluoro-D-glucose (FDG) clearance into muscle and significant increases in the rate constants for inward transport and phosphorylation of FDG [12].

Chemical compound and disease context of SMUG1


Biological context of SMUG1

  • When either UNG1 or SMUG1 functions are reintroduced back into the null strain and then subjected to antifolate treatment, the cells revert back to the wild-type phenotype as shown by a restored sensitivity to drug and S-phase arrest [17].
  • SMUG1 is present at similar levels in cell nuclei of non-proliferating and proliferating tissues, indicating a replication- independent role in DNA repair [18].
  • Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil-DNA glycosylase [18].
  • SMUG1 is able to excise uracil from immunoglobulin genes: insight into mutation versus repair [19].
  • SMUG1, if overexpressed, can partially substitute for UNG to assist antibody diversification as judged by its effect on somatic hypermutation patterns (in both DT40 B cells and mice) as well as a restoration of isotype switching in SMUG-transgenic msh2-/- ung-/- mice [19].

Anatomical context of SMUG1

  • Overexpression of NFI-C in NIH-3T3 cells results in an increase in SMUG1 enzyme activity [20].
  • Northern blot analysis performed on mRNAs derived from different cell lines reveals that the steady-state levels of hSMUG1 transcript are about 10-fold lower relative to UDG [20].
  • The HeLa cell extract and hSMUG1 exhibited a similar damage preference (hoU.G > hmU.A, fU.A), and the activities for fU, hmU, and hoU in the cell extract were effectively neutralized with hSMUG1 antibodies [21].
  • Limbic seizures result in dramatically elevated metabolic activity in the hippocampus, whereas vibrissal stimulation results in more modest increases in FDG uptake in the contralateral neocortex [22].
  • Therefore, preserved wall thickness and systolic wall thickening in regions with moderate reduction in blood flow and FDG activity, and in irreversible 201Tl defects that are only mild-to-moderate, provide additional evidence that such regions represent viable myocardium [23].

Associations of SMUG1 with chemical compounds


Other interactions of SMUG1


Analytical, diagnostic and therapeutic context of SMUG1


  1. Base J, found in nuclear DNA of Trypanosoma brucei, is not a target for DNA glycosylases. Ulbert, S., Eide, L., Seeberg, E., Borst, P. DNA Repair (Amst.) (2004) [Pubmed]
  2. Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase activity as SMUG1. Boorstein, R.J., Cummings, A., Marenstein, D.R., Chan, M.K., Ma, Y., Neubert, T.A., Brown, S.M., Teebor, G.W. J. Biol. Chem. (2001) [Pubmed]
  3. Assessment of axillary lymph node involvement in breast cancer patients with positron emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose. Avril, N., Dose, J., Jänicke, F., Ziegler, S., Römer, W., Weber, W., Herz, M., Nathrath, W., Graeff, H., Schwaiger, M. J. Natl. Cancer Inst. (1996) [Pubmed]
  4. Axillary lymph node staging in breast cancer by 2-fluoro-2-deoxy-D-glucose-positron emission tomography: clinical evaluation and alternative management. Greco, M., Crippa, F., Agresti, R., Seregni, E., Gerali, A., Giovanazzi, R., Micheli, A., Asero, S., Ferraris, C., Gennaro, M., Bombardieri, E., Cascinelli, N. J. Natl. Cancer Inst. (2001) [Pubmed]
  5. Profound underestimation of glucose uptake by [18F]2-deoxy-2-fluoroglucose in reperfused rat heart muscle. Doenst, T., Taegtmeyer, H. Circulation (1998) [Pubmed]
  6. 2-18fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. De Santis, M., Becherer, A., Bokemeyer, C., Stoiber, F., Oechsle, K., Sellner, F., Lang, A., Kletter, K., Dohmen, B.M., Dittrich, C., Pont, J. J. Clin. Oncol. (2004) [Pubmed]
  7. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Herholz, K., Salmon, E., Perani, D., Baron, J.C., Holthoff, V., Frölich, L., Schönknecht, P., Ito, K., Mielke, R., Kalbe, E., Zündorf, G., Delbeuck, X., Pelati, O., Anchisi, D., Fazio, F., Kerrouche, N., Desgranges, B., Eustache, F., Beuthien-Baumann, B., Menzel, C., Schröder, J., Kato, T., Arahata, Y., Henze, M., Heiss, W.D. Neuroimage (2002) [Pubmed]
  8. Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington's disease. Antonini, A., Leenders, K.L., Spiegel, R., Meier, D., Vontobel, P., Weigell-Weber, M., Sanchez-Pernaute, R., de Yébenez, J.G., Boesiger, P., Weindl, A., Maguire, R.P. Brain (1996) [Pubmed]
  9. Regional cerebral glucose metabolism in children with deterioration of one or more cognitive functions and continuous spike-and-wave discharges during sleep. Maquet, P., Hirsch, E., Metz-Lutz, M.N., Motte, J., Dive, D., Marescaux, C., Franck, G. Brain (1995) [Pubmed]
  10. Uracil-DNA glycosylase acts by substrate autocatalysis. Dinner, A.R., Blackburn, G.M., Karplus, M. Nature (2001) [Pubmed]
  11. B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil. Kavli, B., Andersen, S., Otterlei, M., Liabakk, N.B., Imai, K., Fischer, A., Durandy, A., Krokan, H.E., Slupphaug, G. J. Exp. Med. (2005) [Pubmed]
  12. The effect of non-insulin-dependent diabetes mellitus and obesity on glucose transport and phosphorylation in skeletal muscle. Kelley, D.E., Mintun, M.A., Watkins, S.C., Simoneau, J.A., Jadali, F., Fredrickson, A., Beattie, J., Thériault, R. J. Clin. Invest. (1996) [Pubmed]
  13. Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil. Findlay, M., Young, H., Cunningham, D., Iveson, A., Cronin, B., Hickish, T., Pratt, B., Husband, J., Flower, M., Ott, R. J. Clin. Oncol. (1996) [Pubmed]
  14. Synthesis and evaluation of 18F-labeled choline as an oncologic tracer for positron emission tomography: initial findings in prostate cancer. DeGrado, T.R., Coleman, R.E., Wang, S., Baldwin, S.W., Orr, M.D., Robertson, C.N., Polascik, T.J., Price, D.T. Cancer Res. (2001) [Pubmed]
  15. Divergent expression of regional metabolic topographies in Parkinson's disease and normal ageing. Moeller, J.R., Eidelberg, D. Brain (1997) [Pubmed]
  16. Changes in regional brain (18)F-fluorodeoxyglucose uptake at hypoglycemia in type 1 diabetic men associated with hypoglycemia unawareness and counter-regulatory failure. Cranston, I., Reed, L.J., Marsden, P.K., Amiel, S.A. Diabetes (2001) [Pubmed]
  17. hSMUG1 can functionally compensate for Ung1 in the yeast Saccharomyces cerevisiae. Elateri, I., Tinkelenberg, B.A., Hansbury, M., Caradonna, S., Muller-Weeks, S., Ladner, R.D. DNA Repair (Amst.) (2003) [Pubmed]
  18. Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil-DNA glycosylase. Nilsen, H., Haushalter, K.A., Robins, P., Barnes, D.E., Verdine, G.L., Lindahl, T. EMBO J. (2001) [Pubmed]
  19. SMUG1 is able to excise uracil from immunoglobulin genes: insight into mutation versus repair. Di Noia, J.M., Rada, C., Neuberger, M.S. EMBO J. (2006) [Pubmed]
  20. The transcription factor, NFI/CTF plays a positive regulatory role in expression of the hSMUG1 gene. Elateri, I., Muller-Weeks, S., Caradonna, S. DNA Repair (Amst.) (2003) [Pubmed]
  21. Mammalian 5-formyluracil-DNA glycosylase. 2. Role of SMUG1 uracil-DNA glycosylase in repair of 5-formyluracil and other oxidized and deaminated base lesions. Masaoka, A., Matsubara, M., Hasegawa, R., Tanaka, T., Kurisu, S., Terato, H., Ohyama, Y., Karino, N., Matsuda, A., Ide, H. Biochemistry (2003) [Pubmed]
  22. In vivo imaging of neuronal activation and plasticity in the rat brain by high resolution positron emission tomography (microPET). Kornblum, H.I., Araujo, D.M., Annala, A.J., Tatsukawa, K.J., Phelps, M.E., Cherry, S.R. Nat. Biotechnol. (2000) [Pubmed]
  23. Regional left ventricular wall thickening. Relation to regional uptake of 18fluorodeoxyglucose and 201Tl in patients with chronic coronary artery disease and left ventricular dysfunction. Perrone-Filardi, P., Bacharach, S.L., Dilsizian, V., Maurea, S., Frank, J.A., Bonow, R.O. Circulation (1992) [Pubmed]
  24. DNA glycosylase recognition and catalysis. Fromme, J.C., Banerjee, A., Verdine, G.L. Curr. Opin. Struct. Biol. (2004) [Pubmed]
  25. Mutational analysis of the damage-recognition and catalytic mechanism of human SMUG1 DNA glycosylase. Matsubara, M., Tanaka, T., Terato, H., Ohmae, E., Izumi, S., Katayanagi, K., Ide, H. Nucleic Acids Res. (2004) [Pubmed]
  26. Myocardial blood flow, glucose uptake, and recruitment of inotropic reserve in chronic left ventricular ischemic dysfunction. Implications for the pathophysiology of chronic myocardial hibernation. Gerber, B.L., Vanoverschelde, J.L., Bol, A., Michel, C., Labar, D., Wijns, W., Melin, J.A. Circulation (1996) [Pubmed]
  27. Metabolic responses of hibernating and infarcted myocardium to revascularization. A follow-up study of regional perfusion, function, and metabolism. Marwick, T.H., MacIntyre, W.J., Lafont, A., Nemec, J.J., Salcedo, E.E. Circulation (1992) [Pubmed]
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