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| mutagenesisSummarySummary: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS. Top Publications
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Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesisMichael A Kohanski
Howard Hughes Medical Institute, Boston University, Boston, MA 02215, USA
Mol Cell 37:311-20. 2010..Here, we show that sublethal levels of bactericidal antibiotics induce mutagenesis, resulting in heterogeneous increases in the minimum inhibitory concentration for a range of antibiotics, ..
Natural mutagenesis of human genomes by endogenous retrotransposonsRebecca C Iskow
Genetics and Molecular Biology Graduate Program, Emory University, Atlanta, GA 30322, USA
Cell 141:1253-61. 2010..technologies are not capable of detecting most of these young insertions, and the true extent of germline mutagenesis by endogenous human retrotransposons has been difficult to examine...
Estimating the per-base-pair mutation rate in the yeast Saccharomyces cerevisiaeGregory I Lang
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Genetics 178:67-82. 2008..44x10(-10) at CAN1) and we propose a definition for the effective target size of genes (the probability that a mutation inactivates the gene) that acknowledges that the mutation rate is nonuniform across the genome...
Increased mutagenesis and unique mutation signature associated with mitotic gene conversionWade M Hicks
Department of Biology and Rosenstiel Center, Brandeis University, Waltham, MA 02454 9110, USA
Science 329:82-5. 2010..These observations suggest that increased DSB frequencies in oncogene-activated mammalian cells may also increase the probability of acquiring mutations required for transition to a cancerous state...
Chromosomal transposition of PiggyBac in mouse embryonic stem cellsWei Wang
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, United Kingdom
Proc Natl Acad Sci U S A 105:9290-5. 2008..The comprehensive information from this study should facilitate further exploration of the potential of PB and SB DNA transposons in mammalian genetics...
Knowledge-based computational mutagenesis for predicting the disease potential of human non-synonymous single nucleotide polymorphismsMajid Masso
Laboratory for Structural Bioinformatics, Department of Bioinformatics and Computational Biology, George Mason University, 10900 University Blvd MS 5B3, Manassas, VA 20110, USA
J Theor Biol 266:560-8. 2010..by quantifying environmental perturbations in the associated proteins with the use of a computational mutagenesis methodology that relies on a four-body, knowledge-based, statistical contact potential...
Retroviral elements and their hosts: insertional mutagenesis in the mouse germ lineIrina A Maksakova
Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada
PLoS Genet 2:e2. 2006..The prevalence of mouse ERV activity indicates that the genome of the laboratory mouse is presently behind in the "arms race" against invasion...
High-resolution melting curve analysis for rapid detection of mutations in a Medaka TILLING libraryTomoko Ishikawa
Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, B4, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
BMC Mol Biol 11:70. 2010..Targeting Induced Local Lesions IN Genomes) is a reverse-genetic strategy that combines random chemical mutagenesis with high-throughput discovery of the induced mutations in target genes...
Structural interpretation of P2X receptor mutagenesis studies on drug actionRichard J Evans
Cell Physiology and Pharmacology, University of Leicester, Leicester, UK
Br J Pharmacol 161:961-71. 2010..b>Mutagenesis based studies have been used to develop an understanding of the molecular basis of their pharmacology with the ..
Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpointDinesh Kumar
Department of Medical Biochemistry and Biophysics, Umea University, SE 90187 Umea, Sweden
Nucleic Acids Res 38:3975-83. 2010..In contrast, when none of the dNTPs was limiting for DNA replication, even extreme and mutagenic dNTP pool imbalances did not activate the S-phase checkpoint and did not interfere with the cell cycle progression...
Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesisMary Mohrin
The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Department of Medicine, Division of Hematology Oncology, University of California San Francisco, San Francisco, CA 94143, USA
Cell Stem Cell 7:174-85. 2010..Our results demonstrate that quiescence is a double-edged sword that renders HSCs intrinsically vulnerable to mutagenesis following DNA damage.
Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modificationMorgan L Maeder
Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
Mol Cell 31:294-301. 2008....
Oxidative damage to DNA: formation, measurement and biochemical featuresJean Cadet
Laboratoire Lesions des Acides Nucleiques, SCIB DRFMC and FRE 2600, CEA Grenoble, F 38054 Grenoble Cedex 9, France
Mutat Res 531:5-23. 2003..For this purpose modified oligonucleotides in which cyclopurine, and cyclopyrimidine nucleosides were site-specifically inserted were synthesized...
In vivo transcriptional profiling of Listeria monocytogenes and mutagenesis identify new virulence factors involved in infectionAna Camejo
IBMC, Instituto de Biologia Molecular e Celular, Group of Molecular Microbiology, Universidade do Porto, Porto, Portugal
PLoS Pathog 5:e1000449. 2009..b>Mutagenesis of in vivo induced genes allowed the identification of novel L...
The ClosTron: Mutagenesis in Clostridium refined and streamlinedJohn T Heap
BBSRC Sustainable BioEnergy Centre, School of Molecular Medical Sciences, Centre for Biomolecular Sciences, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK
J Microbiol Methods 80:49-55. 2010The recent development of the ClosTron Group II intron directed mutagenesis tool for Clostridium has advanced genetics in this genus, and here we present several significant improvements...
A rich TILLING resource for studying gene function in Brassica rapaPauline Stephenson
Department of Crop Genetics, John Innes Centre, Norwich, NR4 7UH, UK
BMC Plant Biol 10:62. 2010..rapa. Moreover, the ongoing sequencing of the B. rapa genome makes this species a highly attractive model for Brassica research and genetic resource development...
FACS-optimized mutants of the green fluorescent protein (GFP)B P Cormack
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305 5402, USA
Gene 173:33-8. 1996..coli, the folding of the mutant proteins is more efficient than folding of wt GFP. These two properties contribute to a greatly increased (100-fold) fluorescence intensity, making the mutants useful for a number of applications...
Herpesvirus of turkey reconstituted from bacterial artificial chromosome clones induces protection against Marek's diseaseSusan J Baigent
Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire RG20 7NN, UK
J Gen Virol 87:769-76. 2006..Using a one-step mutagenesis protocol to delete the essential glycoprotein B gene from the HVT genome, followed by construction of the ..
Generation of a nicking enzyme that stimulates site-specific gene conversion from the I-AniI LAGLIDADG homing endonucleaseAudrey McConnell Smith
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, North Seattle, WA 98109, USA
Proc Natl Acad Sci U S A 106:5099-104. 2009..The development of sequence-specific nicking enzymes like the I-AniI nickase will facilitate comparative analyses of DNA repair and mutagenesis induced by single- or double-strand breaks.
Hierarchy of lesion processing governs the repair, double-strand break formation and mutability of three-lesion clustered DNA damageLaura J Eccles
CRUK MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK
Nucleic Acids Res 38:1123-34. 2010..The inaccurate repair of such clusters has biological significance due to the ultimate risk of tumourigenesis or as potential cytotoxic lesions in tumour cells...
Rab9 GTPase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virusJames L Murray
National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
J Virol 79:11742-51. 2005..By using gene trap insertional mutagenesis, we identified Rab9, which mediates late-endosome-to-trans-Golgi-network trafficking, among several candidate ..
Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprintingMasahiro Kaneda
Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima 411 8540, Japan
Nature 429:900-3. 2004..These results indicate that both Dnmt3a and Dnmt3L are required for methylation of most imprinted loci in germ cells, but also suggest the involvement of other factors...
Regions of the amino terminus of the P2X receptor required for modification by phorbol ester and mGluR1alpha receptorsHairuo Wen
Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK
J Neurochem 108:331-40. 2009..These results demonstrate that the conserved YXTXK/R sequence and a region with a conserved glycine residue close to the first transmembrane segment contribute to PMA and GPCR regulation of P2X(1) receptors...
Cell-to-cell movement of potato potexvirus X is dependent on suppression of RNA silencingElizabeth H Bayne
The Sainsbury Laboratory, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK
Plant J 44:471-82. 2005..It is possible, based on analyses of short interfering RNA accumulation, that P25 suppresses silencing by interfering with either assembly or function of the effector complexes of RNA silencing...
Sanpodo and Notch act in opposition to Numb to distinguish sibling neuron fates in the Drosophila CNSJ B Skeath
Department of Cell and Structural Biology, Howard Hughes Medical Institute, University of Illinois, Urbana, Illinois 61801, USA
Development 125:1857-65. 1998..Taken together, these results show that interactions between sanpodo, the Notch signaling pathway and numb enable CNS sibling neurons to acquire different fates...
Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patientsSteven J Howe
Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, University College London, London, United Kingdom
J Clin Invest 118:3143-50. 2008..Here, we describe the occurrence of clonal T cell acute lymphoblastic leukemia (T-ALL) promoted by insertional mutagenesis in a completed gene therapy trial of 10 SCID-X1 patients...
TILLING in Lotus japonicus identified large allelic series for symbiosis genes and revealed a bias in functionally defective ethyl methanesulfonate alleles toward glycine replacementsJillian Perry
Sainsbury Laboratory, Norwich NR4 7UH, United Kingdom
Plant Physiol 151:1281-91. 2009..Our results demonstrate the power, as well as the limitations, of ethyl methanesulfonate mutagenesis for forward and reverse genetic studies. (Original mutant phenotypes can be accessed at http://data.jic.bbsrc...
Y-family DNA polymerases in Escherichia coliDaniel F Jarosz
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Trends Microbiol 15:70-7. 2007The observation that mutations in the Escherichia coli genes umuC+ and umuD+ abolish mutagenesis induced by UV light strongly supported the counterintuitive notion that such mutagenesis is an active rather than passive process...
Whole-body sleeping beauty mutagenesis can cause penetrant leukemia/lymphoma and rare high-grade glioma without associated embryonic lethalityLara S Collier
Department of Genetics, Masonic Cancer Center and Masonic Cancer Center Histopathology Core, University of Minnesota, Minneapolis, Minnesota, USA
Cancer Res 69:8429-37. 2009..or deletions, indicating that transposon mobilization likely promotes tumor formation by insertional mutagenesis of cancer genes, and not by promoting wide-scale genomic instability...
Mutagenesis of the bacterial RNA polymerase alpha subunit for improvement of complex phenotypesDaniel Klein-Marcuschamer
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Appl Environ Microbiol 75:2705-11. 2009..Although the preferred method has traditionally been mutagenesis and selection, our laboratory has successfully used mutant transcription factors, which direct the RNA ..
A calcineurin-like gene ppb1+ in fission yeast: mutant defects in cytokinesis, cell polarity, mating and spindle pole body positioningT Yoshida
Department of Biophysics, Faculty of Science, Kyoto University, Japan
J Cell Sci 107:1725-35. 1994..Thus the ppb1+ gene appears to be involved in cytokinesis, mating, transport, nuclear and spindle pole body positioning, and cell shape...
Glycosylation broadens the substrate profile of membrane type 1 matrix metalloproteinaseYi I Wu
Department of Cell and Molecular Biology and Division of Hematology Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
J Biol Chem 279:8278-89. 2004..Enzymatic deglycosylation, site-directed mutagenesis, and lectin precipitation assays were used to demonstrate that MT1-MMP contains O-linked complex carbohydrates ..
Premature ageing in mice expressing defective mitochondrial DNA polymeraseAleksandra Trifunovic
Department of Medical Nutrition, Karolinska Institutet, Novum, Karolinska University Hospital, S 141 86 Stockholm, Sweden
Nature 429:417-23. 2004..Our results thus provide a causative link between mtDNA mutations and ageing phenotypes in mammals...
Establishing gene function by mutagenesis in Arabidopsis thalianaLars Østergaard
Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, CA 92093 0116, USA
Plant J 39:682-96. 2004..The first class typically includes point mutations or small deletions derived from chemical or fast neutron mutagenesis whereas the second class includes insertions of transferred-DNA or transposon elements...
Large-scale transposon mutagenesis of Mycoplasma pulmonisChristopher T French
Department of Genetics, University of Alabama Birmingham, Birmingham, AL 35294, USA
Mol Microbiol 69:67-76. 2008..A mutant with a defect in transport of N-acetylglucosamine was identified...
Construction of a self-excisable bacterial artificial chromosome containing the human cytomegalovirus genome and mutagenesis of the diploid TRL/IRL13 geneDong Yu
Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA
J Virol 76:2316-28. 2002..We performed site-directed mutagenesis on pAD/Cre to generate a series of viruses in which the TRL/IRL13 diploid genes were disrupted and subsequently ..
UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinBVeronica G Godoy
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Mol Cell 28:1058-70. 2007..by interaction with these proteins, thereby preventing the template bulging responsible for -1 frameshift mutagenesis. Intriguingly, residues that define the UmuD(2)-interacting surface on DinB statistically covary throughout ..
A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levelsJason W Hickman
Department of Microbiology, Box 357242, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 102:14422-7. 2005..Together, the data suggest that the wsp signal transduction pathway regulates biofilm formation through modulation of cyclic diguanylate levels...
Cloning and expression in Escherichia coli of the OGG1 gene of Saccharomyces cerevisiae, which codes for a DNA glycosylase that excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidineP A Van Der Kemp
Unité de Recherche Associée 147 Centre National de la Recherche Scientifique, Villejuif, France
Proc Natl Acad Sci U S A 93:5197-202. 1996..E. coli (fpg mutY) was transformed by a yeast DNA library, and clones that showed a reduced spontaneous mutagenesis were selected. The antimutator activity was associated with pYSB10, an 11-kbp recombinant plasmid...
Genes required for mycobacterial growth defined by high density mutagenesisChristopher M Sassetti
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA
Mol Microbiol 48:77-84. 2003....
Scanning cysteine mutagenesis analysis of Abeta-(1-40) amyloid fibrilsShankaramma Shivaprasad
Graduate School of Medicine, University of Tennessee, Knoxville, 37920, USA
J Biol Chem 281:993-1000. 2006..Residues 20, 30, and 35, flanking these implicated beta-sandwich regions, are accessible to alkylation in the fibril indicating a location in solvent exposed structure...
Translation elongation factor 1A facilitates the assembly of the tombusvirus replicase and stimulates minus-strand synthesisZhenghe Li
Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, United States of America
PLoS Pathog 6:e1001175. 2010..These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication...
Human RECQ helicases: roles in DNA metabolism, mutagenesis and cancer biologyRaymond J Monnat
Department of Pathology, University of Washington, Seattle, WA 98195 7705, USA
Semin Cancer Biol 20:329-39. 2010..I also discuss the emerging role for RECQ helicases as predictors of disease risk and the response to therapy...
Direct demonstration of half-of-the-sites reactivity in the dimeric cytochrome bc1 complex: enzyme with one inactive monomer is fully active but unable to activate the second ubiquinol oxidation site in response to ligand binding at the ubiquinone reductiMichela Castellani
Institute of Biochemistry, Molecular Genetics, Goethe University and Cluster of Excellence Macromolecular Complexes Frankfurt am Main, D 60438 Frankfurt am Main, Germany
J Biol Chem 285:502-10. 2010....
General mutagenesis of F plasmid TraI reveals its role in conjugative regulationRembrandt J F Haft
Department of Microbiology, University of Washington, Seattle, WA 98195-7242, USA
J Bacteriol 188:6346-53. 2006..Here we report a mutagenesis of the F plasmid relaxase gene traI using in-frame, 31-codon insertions...
A conserved Gly436-Trp-Leu-Ala-Gly-Leu-Phe-Tyr motif in hepatitis C virus glycoprotein E2 is a determinant of CD81 binding and viral entryHeidi E Drummer
The Macfarlane Burnet Institute for Medical Research and Public Health Ltd, GPO Box 2284, Melbourne, Victoria, Australia 3001
J Virol 80:7844-53. 2006..In this study, we used site-directed mutagenesis to examine the functional role of a conserved G436WLAGLFY motif of E2...
Roles of chromosomal and episomal dinB genes encoding DNA pol IV in targeted and untargeted mutagenesis in Escherichia coliS R Kim
Mol Genet Genomics 266:207-15. 2001..Although expression of the dinB gene encoding DNA pol IV is known to result in an enhancement of untargeted mutagenesis, it remains uncertain whether DNA pol IV is involved in a variety of lesion-induced mutagenesis (targeted ..
Genome-wide phenotype analysis in ES cells by regulated disruption of Bloom's syndrome geneKosuke Yusa
Department of Social and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565 0871, Japan
Nature 429:896-9. 2004..Indeed, a combination of N-ethyl-N-nitrosourea mutagenesis and transient loss of Blm expression enabled us to generate an ES cell library with genome-wide bi-allelic ..
Cysteine-scanning mutagenesis of serotonin transporter intracellular loop 2 suggests an alpha-helical conformationYuan Wei Zhang
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520 8066, USA
J Biol Chem 280:30807-13. 2005..A 24-residue region of SERT including IL2, from Ile-270 through Ser-293, was analyzed by cysteine-scanning mutagenesis and chemical modification...
Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesisJesse E Jun
Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian National University, ACT 2601, Canberra, Australia
Immunity 18:751-62. 2003In a genome-wide ENU mouse mutagenesis screen a recessive mouse mutation, unmodulated, was isolated with profound defects in humoral immune responses, selective deficits in B cell activation by antigen receptors and T cell costimulation ..
Cre-lox-based system for multiple gene deletions and selectable-marker removal in Lactobacillus plantarumJolanda M Lambert
Wegeningen Centre for Food Science, Microbial Functionality and Safety Programme, Health and Safety Department, P O Box 20, 6710 BA Ede, The Netherlands
Appl Environ Microbiol 73:1126-35. 2007..First, an effective mutagenesis vector (pNZ5319) was constructed that allows direct cloning of blunt-end PCR products representing homologous ..
Interaction fidelity in two-component signalingHendrik Szurmant
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550N Torrey Pines Road, La Jolla, CA 92037, USA
Curr Opin Microbiol 13:190-7. 2010....
Particulate matter inhibits DNA repair and enhances mutagenesisManju Mehta
Departments of Environmental Medicine, Pathology and Medicine, New York University School of Medicine, Tuxedo, New York 10987, United States
Mutat Res 657:116-21. 2008..We further demonstrated that PM exposure can significantly increase both spontaneous and UV-induced mutagenesis. These results together suggest that the carcinogenicity of PM may act through its combined effect on ..
Spontaneous mutagenesis associated with nucleotide excision repair in Escherichia coliKimiko Hasegawa
Department of Molecular Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630 0192, Japan
Genes Cells 13:459-69. 2008..The repair system itself may thus be an important generator of spontaneous mutation...
Inducible SOS response system of DNA repair and mutagenesis in Escherichia coliCelina Janion
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
Int J Biol Sci 4:338-44. 2008..than forty independent SOS genes, most of which encode proteins engaged in protection, repair, replication, mutagenesis and metabolism of DNA...
Efficient gene targeting in Drosophila by direct embryo injection with zinc-finger nucleasesKelly J Beumer
Department of Biochemistry, University of Utah School of Medicine, 15 North Medical Drive East, Salt Lake City, UT 84112 5650, USA
Proc Natl Acad Sci U S A 105:19821-6. 2008..Both local mutagenesis via nonhomologous end joining (NHEJ) and targeted gene replacement via homologous recombination (HR) have been ..
Functional genetic analysis of the mammalian mitochondrial DNA encoded peptides: a mutagenesis approachMaria Pilar Bayona-Bafaluy
Departamento de Bioquimica y Biologia Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain
Methods Mol Biol 457:379-90. 2008..Chemical mutagenesis followed by mtDNA copy number reduction and the use of large-scale negative selection in duplicate cultures, ..
Analysis by mutagenesis of a chromosomal integron integrase from Shewanella amazonensis SB2BTAndré Larouche
Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Quebec, Quebec, Canada
J Bacteriol 191:1933-40. 2009..Our results also suggest that the cysteine residue in the beta-5 strand is essential to the activity of Shewanella-type integrases, while the cysteine in the beta-4 strand is less important for the excision activity...
Narrowing laccase substrate specificity using active site saturation mutagenesisNirupama Gupta
Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, New Jersey, NJ 07102, USA
Comb Chem High Throughput Screen 12:269-74. 2009..0 times greater when compared to the wild-type after one round of screening. This illustrates that the substrate-binding pocket is highly evolvable for specificity...
Mutagenesis and homology modeling of the Tn21 integron integrase IntI1Carolina Johansson
Department of Medical Biochemistry and Microbiology, Uppsala University, BMC, Box 582, 751 23 Uppsala, Sweden
Biochemistry 48:1743-53. 2009..to interpret the roles of several amino acid residues, four of which were clearly binding assay responsive upon mutagenesis. Notably, we also observed features indicating that IntI1 may be more prone to base-specific contacts with ..
Alanine-shaving mutagenesis to determine key interfacial residues governing the assembly of a nano-cage maxi-ferritinYu Zhang
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore
J Biol Chem 285:12078-86. 2010..from Escherichia coli, a maxi-ferritin made up of 24 subunits, was chosen as the basis for an alanine-shaving mutagenesis study to discover key amino acid residues at symmetry-related protein-protein interfaces that control protein ..
Identification of residues in the drug translocation pathway of the human multidrug resistance P-glycoprotein by arginine mutagenesisTip W Loo
Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada
J Biol Chem 284:24074-87. 2009..To map the residues in the drug translocation pathway, we performed arginine-scanning mutagenesis on all transmembrane (TM) segments (total = 237 residues) of a P-gp processing mutant (G251V) defective in ..
A transposon toolkit for gene transfer and mutagenesis in protozoan parasitesJeziel D Damasceno
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil
Genetica 138:301-11. 2010..The piggyBac and Tn5 transposons have also been shown to mobilize across Plasmodium spp. genomes circumventing the current limitations in the genetic manipulation of these organisms...
Mutagenesis studies of substrate recognition and catalysis in the sortase A transpeptidase from Staphylococcus aureusMatthew L Bentley
Department of Biochemistry and Biophysics and the Johnson Research Foundation, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
J Biol Chem 283:14762-71. 2008..To better understand the individual roles of the residues within this loop, we performed alanine-scanning mutagenesis. Val-168 and Leu-169 were found to be important for substrate recognition, and Glu-171 was also found to be ..
X-ray structure and mutagenesis of the scorpion depressant toxin LqhIT2 reveals key determinants crucial for activity and anti-insect selectivityIzhar Karbat
Department of Plant Sciences, George S Wise Faculty of Life Sciences, and The Daniella Rich Institute for Structural Biology, Tel Aviv University, Tel Aviv 69978, Israel
J Mol Biol 366:586-601. 2007..On the basis of the mutagenesis studies we hypothesize that following binding to the receptor site, the toxin undergoes a conformational change ..
Conditional mutation of an essential putative glycoprotease eliminates autolysis in Staphylococcus aureusLi Zheng
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1971 Commonwealth Ave, St Paul, MN 55108, USA
J Bacteriol 189:2734-42. 2007....
Excision repair is required for genotoxin-induced mutagenesis in mammalian cellsBradford Brooks
Department of Pharmacology and Physiology, The George Washington University Medical Center, 2300 Eye Street Northwest, Washington, DC 20037, USA
Carcinogenesis 29:1064-9. 2008..Although much is known about Cr-induced DNA damage, very little is known about mechanisms of Cr(VI) mutagenesis and the role that DNA repair plays in this process...
Mutagenesis of the phosphate-binding pocket of KDPG aldolase enhances selectivity for hydrophobic substratesManoj Cheriyan
Department of Chemistry, University of Michigan, Ann Arbor 48109, USA
Protein Sci 16:2368-77. 2007..KDPG) aldolase as a biocatalyst, the molecular determinants of substrate specificity were probed by mutagenesis. Our data demonstrate that S184 is located in the substrate-binding pocket and interacts with the phosphate ..
UTILLdb, a Pisum sativum in silico forward and reverse genetics toolMarion Dalmais
Unite de Recherche en Genomique Vegetale, UMR INRA CNRS, rue Gaston Crémieux, 91057 Evry Cedex, France
Genome Biol 9:R43. 2008..UTILLdb can be searched online for TILLING alleles, through the BLAST tool, or for phenotypic information about mutants by keywords...
A large-scale mutagenesis screen to identify seizure-resistant zebrafishScott C Baraban
Epilepsy Research Laboratory in the Department of Neurological Surgery, University of California, San Francisco, California 94143, USA
Epilepsia 48:1151-7. 2007Zebrafish are a vertebrate organism ideally suited to mutagenesis screening strategies. Although a genetic basis for seizure susceptibility and epilepsy is well established, no efforts have been made to study seizure resistance...
Distinct BIR domains of cIAP1 mediate binding to and ubiquitination of tumor necrosis factor receptor-associated factor 2 and second mitochondrial activator of caspasesTemesgen Samuel
Burnham Institute for Medical Research, La Jolla, CA 92037, USA
J Biol Chem 281:1080-90. 2006....
A variant thrombasthenic phenotype associated with compound heterozygosity of integrin beta3-subunit: (Met124Val)beta3 alters the subunit dimerization rendering a decreased number of constitutive active alphaIIbbeta3 receptorsConsuelo Gonzalez-Manchon
Department of Physiopathology and Human Molecular Genetics, Centro de Investigaciones Biologicas CSIC, Ramiro de Maeztu, 9, 28040 Madrid, Spain
Thromb Haemost 92:1377-86. 2004..The substitution of (124Met)beta3 by either a polar or a positively charged amino acid restored the surface exposure and function of the alphaIIbbeta3 receptors whereas a negatively charged residue did not...
Mutational analysis of the helix-turn-helix region of Bacillus subtilis response regulator DegU, and identification of cis-acting sequences for DegU in the aprE and comK promotersKana Shimane
Department of Marine Science and Technology, Tokai University, 3 20 1 Shimizu Orido, Shizuoka 424 8610, Japan
J Biochem 136:387-97. 2004..Alanine-scanning mutagenesis of the helix-turn-helix region of DegU and in vivo examination of 27 DegU variants revealed five common mutants ..
Structure-guided mutational analysis of the nucleotidyltransferase domain of Escherichia coli NAD+-dependent DNA ligase (LigA)Hui Zhu
Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
J Biol Chem 280:12137-44. 2005..Structure activity relationships were determined by conservative mutagenesis for the Glu-173, Arg-200, Arg-208, and Arg-277 side chains, as well as four other essential side chains that ..
DTL, the Drosophila homolog of PIMT/Tgs1 nuclear receptor coactivator-interacting protein/RNA methyltransferase, has an essential role in developmentOrban Komonyi
Department of Genetics and Molecular Biology, University of Szeged, Közép fasor 52, H 6726 Szeged, Hungary
J Biol Chem 280:12397-404. 2005..Interestingly, two transgenes bearing a mutation in uORF or dORF in trans can result in complete rescue...
Mutational analysis of TraM correlates oligomerization and DNA binding with autoregulation and conjugative DNA transferJun Lu
Department of Biological Sciences, CW405 Biological Sciences Building, University of Alberta, Edmonton, Alberta T6G 2E9, Canada
J Biol Chem 279:55324-33. 2004..we used a two-plasmid system to screen for autoregulation-defective traM mutants generated by random PCR mutagenesis. A total of 72 missense mutations in TraM affecting autoregulation were selected, all of which also resulted in ..
Iron-induced oligomerization of yeast frataxin homologue Yfh1 is dispensable in vivoKerman Aloria
Department of Biochemistry, University of Wisconsin Madison, 433 Babcock Drive, Madison, Wisconsin 53706, USA
EMBO Rep 5:1096-101. 2004..Rather, the capacity of this oligomerization-deficient mutant to interact with the Isu protein suggests a more direct role of Yfh1 in iron-sulphur cluster biogenesis...
Functional studies of the Mycobacterium tuberculosis iron-dependent regulatorC James Chou
Department of Chemistry, University of Washington, Seattle, WA 98195, USA
J Biol Chem 279:53554-61. 2004..Interestingly, the natural IdeR cofactor, Fe(2+), shows high affinities toward both binding sites. These results provide insight into the possible roles for each metal binding site in IdeR activation...
Functional characterization of the yeast Ppz1 phosphatase inhibitory subunit Hal3: a mutagenesis studyIvan Munoz
Department de Bioquimica i Biologia Molecular, Universitat Autonoma de Barcelona, Cerdanyola 08193, Barcelona, Spain
J Biol Chem 279:42619-27. 2004..Although it contains a putative protein phosphatase 1c binding-like sequence (263KLHVLF268), mutagenesis analysis suggests that this motif is not required for Ppz1 binding and inhibition...
Closely related mammals have distinct asialoglycoprotein receptor carbohydrate specificitiesEric I Park
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
J Biol Chem 279:40954-9. 2004..0 and 1.0:1.0, respectively. Mutagenesis was used to show that amino acids both in the immediate vicinity of the proposed binding site for terminal ..
Cysteine-scanning mutagenesis and disulfide mapping studies of the conserved domain of the twin-arginine translocase TatB componentPhilip A Lee
Department of Molecular Microbiology, John Innes Centre, Norwich NR4 7UH, United Kingdom
J Biol Chem 281:34072-85. 2006..Our results suggest that the transmembrane helices of TatB protomers are in the center rather than the periphery of the TatBC complex...
Structure and function of both domains of ArnA, a dual function decarboxylase and a formyltransferase, involved in 4-amino-4-deoxy-L-arabinose biosynthesisGareth J Williams
Centre for Biomolecular Science, The University of St Andrews, UK
J Biol Chem 280:23000-8. 2005..Our data suggest that the decarboxylase domain catalyzes both hydride abstraction (oxidation) from the C-4' position and the subsequent decarboxylation...
Crystal structure of the HP1-EMSY complex reveals an unusual mode of HP1 bindingYing Huang
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
Structure 14:703-12. 2006..This structural information expands our understanding of HP1 binding specificity and provides insights into interactions between HP1 homodimers that are likely to be important for heterochromatin formation...
Role of transmembrane segment 10 in efflux mediated by the staphylococcal multidrug transport protein QacAZhiqiang Xu
School of Biological Sciences, University of Sydney, New South Wales, Australia
J Biol Chem 281:792-9. 2006..importance of transmembrane segment 10, which is thought to be involved in substrate binding, cysteine-scanning mutagenesis was performed in which 35 amino acid residues in the putative transmembrane helix and its flanking regions were ..
Single amino acid substitution in the PC1/3 propeptide can induce significant modifications of its inhibitory profile toward its cognate enzymeNadia Rabah
Neuropeptides Structure and Metabolism, Institut de Recherches Cliniques de Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 281:7556-67. 2006....
Bacterial cell killing mediated by topoisomerase I DNA cleavage activityBokun Cheng
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA
J Biol Chem 280:38489-95. 2005..From sequence analysis and site-directed mutagenesis, it was determined that a single amino acid substitution in the TOPRIM domain changing a strictly conserved ..
CK2-dependent C-terminal phosphorylation at T300 directs the nuclear transport of TSPY proteinRoswitha Krick
Institute of Human Genetics, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany
Biochem Biophys Res Commun 341:343-50. 2006..Using various combinations of in vitro mutagenesis and enhanced green fluorescent protein reporter gene-expression experiments we were able to show that while the ..
Distinct contributions of KH domains to substrate binding affinity of Drosophila P-element somatic inhibitor proteinNikolas H Chmiel
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
RNA 12:283-91. 2006..These results show that despite the ability of a single KH domain to bind RNA in some systems, PSI requires multiple tandem KH domains for specific and high-affinity recognition of substrate RNA...
Chemical genetic engineering of G protein-coupled receptor kinase 2Denise M Kenski
Chemistry and Chemical Biology Graduate Program, Department of Psychiatry, University of California, San Francisco, California 94143, USA
J Biol Chem 280:35051-61. 2005..These results suggest there is a difference in the GRK requirement for initial ligand-induced internalization of a G protein-coupled receptor compared with subsequent rounds of reinternalization...
Unique substrate recognition by botulinum neurotoxins serotypes A and ESheng Chen
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
J Biol Chem 281:10906-11. 2006..The basis for this extended substrate recognition and specificity is unclear. Saturation mutagenesis and deletion mapping identified residues 156-202 of SNAP25 as the optimal cleavage domain for BoNT/A, whereas ..
Mutations in the dimerization domain of the b subunit from the Escherichia coli ATP synthase. Deletions disrupt function but not enzyme assemblyDaniel J Cipriano
Department of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
J Biol Chem 281:12408-13. 2006..This function is proposed to depend on proper, specific interactions between the b subunits and F1...
Fine tuning of the specificity of an anti-progesterone antibody by first and second sphere residue engineeringOlivier Dubreuil
, , , , Centre d'Etudes de Saclay, Gif-sur-Yvette Cedex 91191, France
J Biol Chem 280:24880-7. 2005..of anti-progesterone P15G12C12G11 antibody was improved by combination of in vitro scanning saturation mutagenesis and error-prone PCR...
Structural and functional dissection of the Abp1 ADFH actin-binding domain reveals versatile in vivo adapter functionsOmar Quintero-Monzon
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454, USA
Mol Biol Cell 16:3128-39. 2005..cerevisiae Abp1 actin-binding actin depolymerizing factor homology (ADFH) domain and dissect its activities by mutagenesis. Abp1-ADFH domain and ADF/cofilin structures are similar, and they use conserved surfaces to bind actin; ..
Characterization of the interaction between interleukin-13 and interleukin-13 receptorsKazuhiko Arima
Division of Medical Biochemistry, Department of Biomolecular Sciences, Center for Comprehensive Community Medicine, Saga Medical School, Saga 849 8501, Japan
J Biol Chem 280:24915-22. 2005..These results provide the basis for a precise understanding of the interaction between IL-13 and its receptors...
Mechanistic insights into the isochorismate pyruvate lyase activity of the catalytically promiscuous PchB from combinatorial mutagenesis and selectionDominik E Künzler
Laboratorium fur Organische Chemie, Swiss Federal Institute of Technology ETH, CH 8093 Zurich, Switzerland
J Biol Chem 280:32827-34. 2005..The experiments demonstrate that focusing directed evolution strategies on the readily accessible surrogate activity of an enzyme can provide valuable insights into the mechanism of the primary reaction...
Interactive sites in the MyD88 Toll/interleukin (IL) 1 receptor domain responsible for coupling to the IL1beta signaling pathwayChunsheng Li
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232 2363, USA
J Biol Chem 280:26152-9. 2005..Mutations in Box 2 and 3 prevented homotypic MyD88 oligomerization via TIR domain. Based on this structure-function analysis, a three-dimensional docking model of TIR-TIR interaction between MyD88 and IL1RAcP was developed...
Substituted cysteine accessibility of the third transmembrane domain of the creatine transporter: defining a transport pathwayJoanna R Dodd
Cell Biology and Biochemistry Section, School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
J Biol Chem 280:32649-54. 2005..The background for mutagenesis was a C144S mutant retaining approximately 75% of wild-type transport activity but resistant to ..
The function of the small insertion in the hinge subdomain in the control of constitutive mammalian nitric-oxide synthasesRachel J Jones
Department of Biology, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA
J Biol Chem 279:36876-83. 2004..Taken together, these results suggest that the small insertion protects the calmodulin binding site and that it may be a modulator of NOS activity...
Four N-linked glycosylation sites in human toll-like receptor 2 cooperate to direct efficient biosynthesis and secretionAlexander N R Weber
RA Pharmacology, RI CEDD, GlaxoSmithKline Medicines Research Centre, Stevenage SG1 2NY, United Kingdom
J Biol Chem 279:34589-94. 2004..Using site-directed mutagenesis, we have found that in Toll-like receptor 2 extracellular domain all four predicted glycosylation sites are ..
Crystal structure of an in vitro affinity- and specificity-matured anti-testosterone Fab in complex with testosterone. Improved affinity results from small structural changes within the variable domainsJarkko Valjakka
Department of Chemistry, University of Joensuu, P O Box 111, Finland
J Biol Chem 277:44021-7. 2002..has been generated by stepwise optimization of the complementarity-determining regions (CDRs) by random mutagenesis and phage display selection of a monoclonal antibody (3-C(4)F(5))...
Identification of a conserved sequence motif that promotes Cdc37 and cyclin D1 binding to Cdk4Qiang Zhao
Department of Oncology, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA
J Biol Chem 279:12560-4. 2004..We first determined, using in vitro assays, that Cdc37 binds to the amino-terminal lobe of Cdk4. Subsequent mutagenesis revealed that Gly-15 (G15A) and Gly-18 (G18A) were critical for Cdc37-Cdk4 complex formation...
Research Grants
- STRUCTURE, BIOSYNTHESIS AND FUNCTION OF GLYCOPROTEINSStuart Kornfeld; Fiscal Year: 2007..We will use site-directed mutagenesis to identify residues on the surface of DNase I that determine binding to phosphotransferase and analyze how ..
- CHARACTERIZATION OF NEUROPILIN, A NOVEL VEGF RECEPTORMichael Klagsbrun; Fiscal Year: 2007..whether these ligand binding sites are unique or overlapping by analysis of deletion mutants and site-directed mutagenesis; ii) structural analysis of the heparin that binds NRP blb2 in collaboration with Dr John Gallagher (University ..
- REACTION MECHANISM OF MYOCARDIAC UBIQUINONE-PROTEINSChang An Yu; Fiscal Year: 2007..During past support periods we have established protocols for site-directed mutagenesis coupled with in vivo and in vitro reconstitutionto study some of the structural and functional relationships in ..
- The role of human DNA polymerase eta in the mutagenic response to oxidative stresSCOTT MCCULLOCH; Fiscal Year: 2009..A similar logic has been proposed for the suppression of mutagenesis during pol 7 dependent bypass of 8-oxo-dG...
- The role of human DNA polymerase eta in the mutagenic response to oxidative stresSCOTT DAVID MCCULLOCH; Fiscal Year: 2010..A similar logic has been proposed for the suppression of mutagenesis during pol 7 dependent bypass of 8-oxo-dG...
- MECHANISMS IN THE REGULATION OF SP-A GENE EXPRESSIONCAROLE MENDELSON; Fiscal Year: 2007..In deletion mapping and mutagenesis studies, we have found that basal and cAMP induction of rabbit and human SP-A promoter activity is critically ..
- Monoamine Transporter Structure-Function StudiesCHRISTOPHER SURRATT; Fiscal Year: 2007..create LeuTAa-based 3-D DAT and SERT models, and use the models to identify and characterize via site-directed mutagenesis and pharmacology the DAT and SERT residues key in substrate (e.g...
- Genetic Basis of Myeloid Neoplasia--Mutagenesis ScreensA Look; Fiscal Year: 2005..This proposal tests two linked hypotheses: (i) genome-wide ethylnitrosourea (ENU) mutagenesis screens in the zebrafish can be used to identify dominant and recessive mutations that cause a deficiency or ..
- OXIDATIVE ACTIVATION OF QUINONES AND MUTAGENESISDhrubajyoti Chakravarti; Fiscal Year: 2002..hypothesize that these carcinogens (diethylstilbestrol and benzene) and dopamine cause disease through specific mutagenesis, induce mutations by error-prone repair...
- MUTAGENESIS OF SPECIFIC REGIONS OF THE SV 40 GENOMEMARY TEVETHIA; Fiscal Year: 2001....
- Genetic analysis of Cryptococcus neoformans virulenceJoseph Heitman; Fiscal Year: 2009..We propose to broadly apply Insertional mutagenesis to identify genes encoding virulence attributes necessary for infection. C...
- Genetic analysis of Cryptococcus neoformans virulenceJoseph Heitman; Fiscal Year: 2007..We propose to broadly apply Insertional mutagenesis to identify genes encoding virulence attributes necessary for infection. C...
- Error Correction in DNA Synthesis: A Biochemical StudyMYRON FREDRIC GOODMAN; Fiscal Year: 2011..While investigating the biochemical basis of SOS damaged- induced mutagenesis in E...
- VOLTAGE-SENSITIVE SODIUM CHANNELS IN BRAINWilliam Catterall; Fiscal Year: 1993..Structure-function studies with site-directed antibodies and site-directed mutagenesis have identified regions of the channel that are critical for voltage-dependent activation, fast channel ..
- ANTICHYMOTRYPSIN INTERACTION WITH SERINE PROTEASESBARRY COOPERMAN; Fiscal Year: 1993..interaction of ACT with Chtr and CatG, and to test our understanding by redesigning ACT, through site-specific mutagenesis, to change its specificity...
- MUTAGENESIS OF PYRIDOXAL PHOSPHATE-DEPENDENT ENZYMESJACK KIRSCH; Fiscal Year: 1993..Site directed mutagenesis of aspartate aminotransferase will be based on computer modeling of the two homologous structures...
- TRANSCRIPTION/REPLICATION OF NEGATIVE STRAND RNA VIRUSESSue Moyer; Fiscal Year: 1999..We have located the L binding domain on P protein and propose to do site-directed mutagenesis in this domain of P to identify the amino acids critical for binding and RNA synthesis...
- SITE-SPECIFIC MUTAGENESIS OF ISOMERASESGregory Petsko; Fiscal Year: 1993The goal of this project is to use a combination of site-directed mutagenesis and X-ray crystallography to understand the structural basis of the catalytic power of yeast triosephosphate isomerase (TIM) and to unravel the mechanism of ..
- L1 retrotransposon-based mutagenesis for rat models of human diseasesEric Ostertag; Fiscal Year: 2007..Unfortunately, many genetic manipulation techniques available in the mouse such as random mutagenesis with a gene trap (both retroviral-based and non-retroviral-based), gene knock- outs, gene knock-ins, and ..
- Experimental viral evolution at high mutation rateJAMES JEFFREY BULL; Fiscal Year: 2010..of deleterious mutations;high rates can even cause population extinction, a process known as lethal mutagenesis. This principle underlies the common use of mutagenic, drugs to treat viral infections clinically...
- Zebrafish ES cell lines for targeted mutagenesisPaul Collodi; Fiscal Year: 2010..Although large-scale forward mutagenesis screens have been successfully applied to the zebrafish to identify genes that regulate early development and ..
- Zebrafish ES cell lines for targeted mutagenesisPaul Collodi; Fiscal Year: 2009..Although large-scale forward mutagenesis screens have been successfully applied to the zebrafish to identify genes that regulate early development and ..
- MOLECULAR GENETICS AND MECHANISM OF PROTEIN ANTIBIOTICSJ Hansen; Fiscal Year: 1993..Recent studies in this laboratory have used site-directed mutagenesis of the subtilin prepeptide gene to construct and express a structural analog of subtilin, in which the change ..
- MOLECULAR GENETICS AND MECHANISM OF PROTEIN ANTIBIOTICSJ Hansen; Fiscal Year: 2001..Recent studies in this laboratory have used site-directed mutagenesis of the subtilin prepeptide gene to construct and express a structural analog of subtilin, in which the change ..
