Disease relevance of SMUG1

• No excision of J was found, but 5-HmU was excised by AlkA and Mug from Escherichia coli and by human SMUG1 and TDG, confirming previous reports [1].
• Purification from calf thymus of a DNA N-glycosylase activity (HMUDG) that released 5-hydroxymethyluracil (5hmUra) from the DNA of Bacillus subtilis phage SPO1 was undertaken [2].
• CONCLUSIONS: PET imaging with F-18 FDG allowed accurate and noninvasive detection of axillary lymph node metastases, primarily in patients with breast cancer more advanced than stage pT1 [3].
• In this study, we evaluated whether an alternative, noninvasive method--i.e., positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-- could be used to determine axillary lymph node status in patients with breast cancer [4].
• In the fasted state, however, FDG overestimates glucose uptake during ischemia [5].

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

• Positron emission tomography (PET) imaging with the radiolabeled glucose analogue 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-18 FDG) has been used to visualize primary breast tumors as well as bone and soft-tissue metastases [3].
• PURPOSE: To investigate and measure the metabolism of colorectal cancer liver metastases using 18F-fluorodeoxyglucose positron emission tomography (FDG PET), before and during the first month of chemotherapy [13].
• Accumulation of FCH and FDG were comparable in cultured prostate cancer cells, whereas only FCH was inhibited (90%) by hemicholinium-3, a specific inhibitor of choline transport and phosphorylation [14].
• We have used [18F]fluorodeoxyglucose (FDG) with PET to identify regional metabolic covariance patterns associated with Parkinson's disease and normal ageing [15].
• Hypoglycemia-unaware patients were asymptomatic during hypoglycemia, with marked attenuation of their epinephrine responses (mean [+/- SD] peak of 0.77 +/- 0.39 vs. 7.52 +/- 2.9 nmol/l; P < 0.0003) and a reduced global brain FDG uptake ([mean +/- SE] 2.592 +/- 0.188 vs. 2.018 +/- 0.174 at euglycemia; P = 0.027) [16].

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

• Mammalian 5-formyluracil-DNA glycosylase. 2. Role of SMUG1 uracil-DNA glycosylase in repair of 5-formyluracil and other oxidized and deaminated base lesions [21].
• These organisms lack a SMUG1 homologue and use a single enzyme, Ung1 to carry out uracil-repair [17].
• SMUG1 also has the capacity to excise oxidized pyrimidine bases such as 5-hydroxymethyluracil and 5-formyluracil from DNA [20].
• The NMR structure of 3-methyladenine glycosylase I revealed its place among the structural families of DNA glycosylases and the X-ray structure of SMUG1 likewise confirmed that this protein is a member of the uracil DNA glycosylase superfamily [24].
• Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase activity as SMUG1 [2].

Other interactions of SMUG1

• Family-3 (SMUG1) enzymes have recently been identified and have a preference for uracil in single-stranded DNA when assayed in vitro [17].

Analytical, diagnostic and therapeutic context of SMUG1

• In the present study, we used site-directed mutagenesis to construct a series of mutants of human SMUG1 (hSMUG1), and tested their activity for uracil, hoU, hmU, fU and other bases to elucidate the catalytic and damage-recognition mechanism of hSMUG1 [25].
• Twenty-five patients with chronic stable coronary artery disease and left ventricular dysfunction (ejection fraction, 28 +/- 10) underwent exercise 201Tl tomographic imaging (SPECT), using a reinjection protocol, positron emission tomography (PET) with FDG and H2(15)O, and gated MRI [23].
• CONCLUSIONS: This study indicates that chronic but reversible ischemic dysfunction is associated with almost normal resting myocardial perfusion, with maintained FDG uptake, and with recruitable inotropic reserve [26].
• Sixteen patients with previous infarction were studied before and after revascularization by myocardial perfusion imaging using 82Rb positron emission tomography, digitized two-dimensional echocardiography, and imaging of postexercise FDG uptake [27].
• FDG uptake decreased significantly with reperfusion in groups 2 and 3, and there was a striking fall in the LC (from >1.0 to <0.2, P<.001) [5].

References