Genomes and Genes
uracil dna glycosidase
Summary: An enzyme that catalyzes the HYDROLYSIS of the N-glycosidic bond between sugar phosphate backbone and URACIL residue during DNA synthesis.
- Schomacher L, Smolorz S, Ciirdaeva E, Ber S, Kramer W, Fritz H. Helix-hairpin-helix protein MJ1434 from Methanocaldococcus jannaschii and EndoIV homologue TTC0482 from Thermus thermophilus HB27 do not process DNA uracil residues. Nucleic Acids Res. 2010;38:5119-29 pubmed publisher..We propose that the uracil processing activities formerly found were due to contaminations with Ung enzyme. Use of Deltaung-strains as hosts for production of putatively DNA-U processing enzymes provides a simple safeguard. ..
- Deslee G, Adair Kirk T, Betsuyaku T, Woods J, Moore C, Gierada D, et al. Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts. Am J Respir Cell Mol Biol. 2010;43:576-84 pubmed publisher..Together, our results demonstrate ROS-dependent, cigarette smoke-induced nucleic-acid oxidation in alveolar fibroblasts, which may play a role in the pathogenesis of emphysema. ..
- Stern Ginossar N, Saleh N, Goldberg M, Prichard M, Wolf D, Mandelboim O. Analysis of human cytomegalovirus-encoded microRNA activity during infection. J Virol. 2009;83:10684-93 pubmed publisher..Thus, we suggest that in addition to miR-UL112, two additional HCMV miRNAs control the life cycle of the virus. ..
- Fortier S, Yang X, Wang Y, Bennett R, Strauss P. Base excision repair in early zebrafish development: evidence for DNA polymerase switching and standby AP endonuclease activity. Biochemistry. 2009;48:5396-404 pubmed publisher..The switch to normal, adult BER occurs fully when the embryos hatch from the chorionic membrane and encounter normal oxidative stress. ..
- Kracker S, Gardès P, Durandy A. Inherited defects of immunoglobulin class switch recombination. Adv Exp Med Biol. 2010;685:166-74 pubmed..Novel findings are awaited from the study ofyet-genetically undefined CSR-deficiencies, probably leading to the identification of AID cofactor(s) and/or proteins involved in CSR-induced DNA repair. ..
- Maul R, Gearhart P. Controlling somatic hypermutation in immunoglobulin variable and switch regions. Immunol Res. 2010;47:113-22 pubmed publisher..The frequency and proximity of these dU nucleotides then in turn inhibit faithful repair and promote strand breaks. ..
- Kunz C, Focke F, Saito Y, Schuermann D, Lettieri T, Selfridge J, et al. Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5-fluorouracil. PLoS Biol. 2009;7:e91 pubmed publisher..The status of TDG expression in a cancer is therefore likely to determine its response to 5-FU-based chemotherapy. ..
- Hinz A, Wang Y, Smerdon M. Base excision repair in a glucocorticoid response element: effect of glucocorticoid receptor binding. J Biol Chem. 2010;285:28683-90 pubmed publisher..These results highlight the potential for both positive and negative impacts of DNA-transcription factor binding on the rate of BER. ..
- Bogani F, Corredeira I, Fernandez V, Sattler U, Rutvisuttinunt W, Defais M, et al. Association between the herpes simplex virus-1 DNA polymerase and uracil DNA glycosylase. J Biol Chem. 2010;285:27664-72 pubmed publisher..These findings support the existence of a viral repair complex that may be capable of replication-coupled base excision repair and further highlight the role of DNA repair in the maintenance of the HSV-1 genome...
- Chung S, Parker J, Bianchet M, Amzel L, Stivers J. Impact of linker strain and flexibility in the design of a fragment-based inhibitor. Nat Chem Biol. 2009;5:407-13 pubmed publisher..Such effects are not apparent from inspection of structures and underscore the importance of linker optimization in fragment-based drug discovery efforts. ..
- Kumar S, Aninat C, Michaux G, Morel F. Anticancer drug 5-fluorouracil induces reproductive and developmental defects in Caenorhabditis elegans. Reprod Toxicol. 2010;29:415-20 pubmed publisher..Thus, we proposed that C. elegans could be a useful model system for studying the mechanisms by which 5-FU might affect either embryo, adult or organ development...
- Ward T, Williams M, Traina Dorge V, Gray W. The simian varicella virus uracil DNA glycosylase and dUTPase genes are expressed in vivo, but are non-essential for replication in cell culture. Virus Res. 2009;142:78-84 pubmed publisher..Further studies will evaluate the pathogenesis of SVV dUTPase and UDG mutants and their potential as varicella vaccines...
- Zharkov D, Mechetin G, Nevinsky G. Uracil-DNA glycosylase: Structural, thermodynamic and kinetic aspects of lesion search and recognition. Mutat Res. 2010;685:11-20 pubmed publisher..Search for the lesion by UNG involves random sliding along DNA alternating with dissociation-association events and partial eversion of undamaged bases for initial sampling. ..
- Bharti S, Varshney U. Analysis of the impact of a uracil DNA glycosylase attenuated in AP-DNA binding in maintenance of the genomic integrity in Escherichia coli. Nucleic Acids Res. 2010;38:2291-301 pubmed publisher..We discuss these findings in the context of a proposal that the residency of DNA glycosylase(s) onto the AP-sites they generate shields them until recruitment of AP-endonucleases for further repair. ..
- Briggs A, Stenzel U, Meyer M, Krause J, Kircher M, Paabo S. Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA. Nucleic Acids Res. 2010;38:e87 pubmed publisher..In addition, our results demonstrate that Neandertal DNA retains in vivo patterns of CpG methylation, potentially allowing future studies of gene inactivation and imprinting in ancient organisms...
- Aghamohammadi A, Parvaneh N, Rezaei N, Moazzami K, Kashef S, Abolhassani H, et al. Clinical and laboratory findings in hyper-IgM syndrome with novel CD40L and AICDA mutations. J Clin Immunol. 2009;29:769-76 pubmed publisher..There are several patients with HIGM phenotype, in which the underlying genetic defects remain to be identified. Other defects such as those in components of the mismatch repair mechanism could be potential candidates for the latter. ..
- Lyons D, O Brien P. Human base excision repair creates a bias toward -1 frameshift mutations. J Biol Chem. 2010;285:25203-12 pubmed publisher..Single nucleotide deletion is predicted to repair +1 frameshift events, but to make -1 frameshift events permanent. Therefore, these findings suggest an additional factor contributing to the bias toward deletion mutations. ..
- Strang B, Coen D. Interaction of the human cytomegalovirus uracil DNA glycosylase UL114 with the viral DNA polymerase catalytic subunit UL54. J Gen Virol. 2010;91:2029-33 pubmed publisher..Our data are consistent with a direct UL114-UL54 interaction, and suggest that UL114 and UL54 act in concert during base excision repair of the viral genome...
- Cole H, Tabor Godwin J, Hayes J. Uracil DNA glycosylase activity on nucleosomal DNA depends on rotational orientation of targets. J Biol Chem. 2010;285:2876-85 pubmed publisher..Our results indicate that some sites within the nucleosome core and the extra-core (linker) DNA regions represent hot spots for repair that could influence critical biological processes. ..
- Pulukuri S, Knost J, Estes N, Rao J. Small interfering RNA-directed knockdown of uracil DNA glycosylase induces apoptosis and sensitizes human prostate cancer cells to genotoxic stress. Mol Cancer Res. 2009;7:1285-93 pubmed publisher..Taken together, these findings indicate that RNA interference-directed targeting of UNG is a convenient, novel tool for studying the biological role of UNG and raises the potential of its application for prostate cancer therapy. ..
- Chien C, Chou C, Su J. Ung1p-mediated uracil-base excision repair in mitochondria is responsible for the petite formation in thymidylate deficient yeast. FEBS Lett. 2009;583:1499-504 pubmed publisher..We propose that the initiation of Ung1p-mediated base excision repair in the uracil-laden mitochondrial genome in a cdc21-1 mutant is responsible for the mitochondrial petite mutations. ..
- Wanner R, Castor D, Güthlein C, Bottger E, Springer B, Jiricny J. The uracil DNA glycosylase UdgB of Mycobacterium smegmatis protects the organism from the mutagenic effects of cytosine and adenine deamination. J Bacteriol. 2009;191:6312-9 pubmed publisher..Together with Ung-type uracil glycosylase, M. smegmatis UdgB also helps attenuate the cytotoxicity of the antimicrobial agent 5-fluorouracil. ..
- Knaevelsrud I, Slupphaug G, Leiros I, Matsuda A, Ruoff P, Bjelland S. Opposite-base dependent excision of 5-formyluracil from DNA by hSMUG1. Int J Radiat Biol. 2009;85:413-20 pubmed publisher..The predominant T --> G and T --> A transversions induced by fU in mammalian cells may be explained by replicative incorporation of C and T, respectively, opposite the lesion and subsequent SMUG1-initiated repair of fU. ..
- Córdoba Cañero D, Dubois E, Ariza R, Doutriaux M, Roldan Arjona T. Arabidopsis uracil DNA glycosylase (UNG) is required for base excision repair of uracil and increases plant sensitivity to 5-fluorouracil. J Biol Chem. 2010;285:7475-83 pubmed publisher..These results suggest that AtUNG excises uracil in vivo but generates toxic AP sites when processing abundant U:A pairs in dTTP-depleted cells. Altogether, our findings point to AtUNG as the major UDG activity in Arabidopsis. ..
- Knævelsrud I, Moen M, Grøsvik K, Haugland G, Birkeland N, Klungland A, et al. The hyperthermophilic euryarchaeon Archaeoglobus fulgidus repairs uracil by single-nucleotide replacement. J Bacteriol. 2010;192:5755-66 pubmed publisher..The finding that repair product formation is stimulated similarly by ATP and ADP in vitro raises the question of whether ADP is more important in vivo because of its higher heat stability. ..
- Auerbach P, Demple B. Roles of Rev1, Pol zeta, Pol32 and Pol eta in the bypass of chromosomal abasic sites in Saccharomyces cerevisiae. Mutagenesis. 2010;25:63-9 pubmed publisher..RAD30 appeared to be unnecessary for mutagenesis in response to abasic sites, as deleting this gene caused no significant change in either the mutation rates or the mutational spectra due to glycosylase expression. ..
- Fenard D, Houzet L, Bernard E, Tupin A, Brun S, Mougel M, et al. Uracil DNA Glycosylase 2 negatively regulates HIV-1 LTR transcription. Nucleic Acids Res. 2009;37:6008-18 pubmed publisher..The molecular mechanisms involved in the UNG2 antiviral activity still remain elusive but may rely on the sequestration of specific cellular factor(s) critical for viral transcription. ..
- An Y, Xiao J, Jiang L, Yang X, Yu J, Zhao X. Clinical and molecular characterization of X-linked hyper-IgM syndrome patients in China. Scand J Immunol. 2010;72:50-6 pubmed publisher..These mutations reflect the heterogeneity of CD40L gene, indicating the need for accurate and reliable molecular testing in patients suspected of XHIM. ..
- Ma K, Au S, Waye M. Over-expression of SUMO-1 induces the up-regulation of heterogeneous nuclear ribonucleoprotein A2/B1 isoform B1 (hnRNP A2/B1 isoform B1) and uracil DNA glycosylase (UDG) in hepG2 cells. Cell Biochem Funct. 2009;27:228-37 pubmed publisher..The up-regulation is suggested to be mediated via changes at the translational level or protection from degradation by western blotting and RT-PCR. ..
- Jones K, Roche M, Gantier M, Begum N, Honjo T, CARADONNA S, et al. X4 and R5 HIV-1 have distinct post-entry requirements for uracil DNA glycosylase during infection of primary cells. J Biol Chem. 2010;285:18603-14 pubmed publisher..These differences may result from activation of distinct signaling cascades and/or infection of divergent T-lymphocyte subpopulations. ..
- Boesch P, Ibrahim N, Paulus F, Cosset A, Tarasenko V, Dietrich A. Plant mitochondria possess a short-patch base excision DNA repair pathway. Nucleic Acids Res. 2009;37:5690-700 pubmed publisher..In vivo targeting and in vitro import of GFP fusions showed that the putative UDG encoded by the At3g18 630 locus might be the first enzyme of this mitochondrial pathway in Arabidopsis thaliana. ..
- Krijger P, Langerak P, van den Berk P, Jacobs H. Dependence of nucleotide substitutions on Ung2, Msh2, and PCNA-Ub during somatic hypermutation. J Exp Med. 2009;206:2603-11 pubmed publisher..These findings significantly add to our understanding of SHM and necessitate an update of present SHM models. ..
- Rajagopal D, Maul R, Ghosh A, Chakraborty T, Khamlichi A, Sen R, et al. Immunoglobulin switch mu sequence causes RNA polymerase II accumulation and reduces dA hypermutation. J Exp Med. 2009;206:1237-44 pubmed publisher..We propose that altered DNA structure in the switch region pauses RNA polymerase II and limits access of DNA polymerase eta during hypermutation. ..
- Kaushal P, Talawar R, Varshney U, Vijayan M. Structure of uracil-DNA glycosylase from Mycobacterium tuberculosis: insights into interactions with ligands. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010;66:887-92 pubmed publisher..The interactions of the citrate ion with the protein mimic those of uracil, in addition to providing insights into other possible interactions that inhibitors could be involved in. ..
- Guo C, Zhang X, Fink S, Platzer P, Wilson K, Willson J, et al. Ugene, a newly identified protein that is commonly overexpressed in cancer and binds uracil DNA glycosylase. Cancer Res. 2008;68:6118-26 pubmed publisher..Using deletion constructs, we find that Ugene binds to the first 25 amino acids of the UNG2 NH(2) terminus. We suggest that Ugene induction in cancer may contribute to the cancer phenotype by interacting with the BER pathway. ..
- Darwanto A, Theruvathu J, Sowers J, Rogstad D, Pascal T, Goddard W, et al. Mechanisms of base selection by human single-stranded selective monofunctional uracil-DNA glycosylase. J Biol Chem. 2009;284:15835-46 pubmed publisher..The observed distinct mechanisms of base selection demonstrated for members of the uracil glycosylase family help explain how considerable diversity in chemical lesion repair can be achieved. ..
- Bibeau K, Battista M, Houde V, Brochu M. Fetal adrenal gland alterations in a rat model of adverse intrauterine environment. Am J Physiol Regul Integr Comp Physiol. 2010;298:R899-911 pubmed publisher..All of these alterations could have long-lasting health effects and may, hence, be implicated in the pathogenesis of increased blood pressure and cardiac hypertrophy observed in IUGR adult animals from this model...
- Malshetty V, Jain R, Srinath T, Kurthkoti K, Varshney U. Synergistic effects of UdgB and Ung in mutation prevention and protection against commonly encountered DNA damaging agents in Mycobacterium smegmatis. Microbiology. 2010;156:940-9 pubmed publisher..These observations reveal a synergistic effect of UdgB and Ung in DNA repair, and could have implications for the generation of attenuated strains of Mycobacterium tuberculosis. ..
- Friedman J, Majumdar A, Stivers J. Nontarget DNA binding shapes the dynamic landscape for enzymatic recognition of DNA damage. Nucleic Acids Res. 2009;37:3493-500 pubmed publisher..These results suggest that DNA structure and the spontaneous dynamics of base pairs may drive the evolution of a protein sequence that is tuned to respond to this dynamic regime. ..