Summary: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.

Top Publications

  1. pmc High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells
    Yanfang Fu
    1 Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA 2 Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA 3 Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA 4 Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Biotechnol 31:822-6. 2013
  2. ncbi Genes required for mycobacterial growth defined by high density mutagenesis
    Christopher 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
  3. ncbi Initial sequencing and comparative analysis of the mouse genome
    Robert H Waterston
    Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA
    Nature 420:520-62. 2002
  4. pmc Targeted genome editing across species using ZFNs and TALENs
    Andrew J Wood
    Howard Hughes Medical Institute HHMI, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3204, USA
    Science 333:307. 2011
  5. pmc Natural mutagenesis of human genomes by endogenous retrotransposons
    Rebecca C Iskow
    Genetics and Molecular Biology Graduate Program, Emory University, Atlanta, GA 30322, USA
    Cell 141:1253-61. 2010
  6. ncbi Efficient transposition of the piggyBac (PB) transposon in mammalian cells and mice
    Sheng Ding
    Institute of Developmental Biology and Molecular Medicine, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China
    Cell 122:473-83. 2005
  7. ncbi 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
  8. pmc An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers
    Steven A Roberts
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
    Nat Genet 45:970-6. 2013
  9. pmc Improved somatic mutagenesis in zebrafish using transcription activator-like effector nucleases (TALENs)
    Finola E Moore
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America
    PLoS ONE 7:e37877. 2012
  10. pmc Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis
    Michael A Kohanski
    Howard Hughes Medical Institute, Boston University, Boston, MA 02215, USA
    Mol Cell 37:311-20. 2010

Detail Information

Publications349 found, 100 shown here

  1. pmc High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells
    Yanfang Fu
    1 Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA 2 Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA 3 Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA 4 Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Biotechnol 31:822-6. 2013
    ..Our work demonstrates that RGNs can be highly active even with imperfectly matched RNA-DNA interfaces in human cells, a finding that might confound their use in research and therapeutic applications. ..
  2. ncbi Genes required for mycobacterial growth defined by high density mutagenesis
    Christopher 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
  3. ncbi Initial sequencing and comparative analysis of the mouse genome
    Robert H Waterston
    Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA
    Nature 420:520-62. 2002
  4. pmc Targeted genome editing across species using ZFNs and TALENs
    Andrew J Wood
    Howard Hughes Medical Institute HHMI, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3204, USA
    Science 333:307. 2011
  5. pmc Natural mutagenesis of human genomes by endogenous retrotransposons
    Rebecca 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...
  6. ncbi Efficient transposition of the piggyBac (PB) transposon in mammalian cells and mice
    Sheng Ding
    Institute of Developmental Biology and Molecular Medicine, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China
    Cell 122:473-83. 2005
    ..used for genetic manipulation in lower organisms, including generating transgenic animals and insertional mutagenesis. In contrast, the usage of transposons in mice and other vertebrate systems is still limited due to the lack of ..
  7. ncbi 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...
  8. pmc An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers
    Steven A Roberts
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
    Nat Genet 45:970-6. 2013
    ..We show here that throughout cancer genomes APOBEC-mediated mutagenesis is pervasive and correlates with APOBEC mRNA levels...
  9. pmc Improved somatic mutagenesis in zebrafish using transcription activator-like effector nucleases (TALENs)
    Finola E Moore
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America
    PLoS ONE 7:e37877. 2012
    ..induced DNA mutations at genomic target sites while only a subset of CoDA ZFNs exhibited detectable rates of mutagenesis. TALENs also exhibited higher mutation rates than CoDA ZFNs that had not been pre-screened using a bacterial ..
  10. pmc Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis
    Michael 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, ..
  11. pmc Evidence for APOBEC3B mutagenesis in multiple human cancers
    Michael B Burns
    Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
    Nat Genet 45:977-83. 2013
    ..Here we address whether APOBEC3B is broadly responsible for mutagenesis in multiple tumor types...
  12. pmc Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification
    Morgan L Maeder
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Mol Cell 31:294-301. 2008
    ..In summary, OPEN provides an "open-source" method for rapidly engineering highly active zinc-finger arrays, thereby enabling broader practice, development, and application of ZFN technology for biological research and gene therapy...
  13. ncbi Somatic progenitor cell vulnerability to mitochondrial DNA mutagenesis underlies progeroid phenotypes in Polg mutator mice
    Kati J Ahlqvist
    Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland
    Cell Metab 15:100-9. 2012
    ..MtDNA mutagenesis in mice with defective Polg exonuclease activity also leads to progeroid symptoms, by an unknown mechanism...
  14. ncbi A genetic screen for mutations affecting embryogenesis in zebrafish
    W Driever
    Cardiovascular Research Center, Massachusetts General Hospital, Charlestown 02129, USA
    Development 123:37-46. 1996
    Systematic genome-wide mutagenesis screens for embryonic phenotypes have been instrumental in the understanding of invertebrate and plant development...
  15. pmc Increased mutagenesis and unique mutation signature associated with mitotic gene conversion
    Wade 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...
  16. pmc Targeted DNA mutagenesis for the cure of chronic viral infections
    Joshua T Schiffer
    Fred Hutchinson Cancer Research Center, Vaccine and Infectious Diseases Division, Seattle, Washington, USA
    J Virol 86:8920-36. 2012
    ..We then review issues regarding persistence of HIV-1, HBV, and HSV that are relevant to eradication with genome-altering approaches...
  17. ncbi A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications
    Takeharu Nagai
    Laboratory for Cell Function and Dynamics, Advanced Technology Development Center, Brain Science Institute, RIKEN, 2 1 Hirosawa, Wako City, Saitama, 351 0198, Japan
    Nat Biotechnol 20:87-90. 2002
    ..Over the last several years, mutagenesis studies have improved folding properties of GFP (refs 1,2)...
  18. pmc Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior
    M H Vitaterna
    Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208
    Science 264:719-25. 1994
    ..The power of ENU mutagenesis combined with the ability to clone murine genes by map position provides a generally applicable approach to ..
  19. pmc Mutation as a stress response and the regulation of evolvability
    Rodrigo S Galhardo
    Department of Molecular and Human Genetics, Baylor College, Houston, Texas 77030 3411, USA
    Crit Rev Biochem Mol Biol 42:399-435. 2007
    ..The emerging molecular mechanisms of stress-induced mutagenesis vary but share telling common components that underscore two common themes...
  20. pmc Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis
    A A Shvedova
    Health Effects Laboratory Div, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
    Am J Physiol Lung Cell Mol Physiol 295:L552-65. 2008
    ..SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 mice...
  21. pmc Suppressor mutagenesis identifies a velvet complex remediator of Aspergillus nidulans secondary metabolism
    Mona I Shaaban
    Department of Medical Microbiology and Immunology, University of Wisconsin Madison, Madison, WI 53706, USA
    Eukaryot Cell 9:1816-24. 2010
    ..An intact Velvet complex coupled with an OE::rsmA allele increases SM many fold over the wild-type level, but loss of rsmA does not decrease SM. RsmA encodes a putative bZIP basic leucine zipper-type transcription factor...
  22. pmc β-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity
    A Gutierrez
    INSERM U1001, Universite Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Paris Descartes, Paris, France
    Nat Commun 4:1610. 2013
    ..concentrations of β-lactam antibiotics cause reactive oxygen species production and induce PolIV-dependent mutagenesis in Escherichia coli...
  23. pmc Activity-enhancing mutations in an E3 ubiquitin ligase identified by high-throughput mutagenesis
    Lea M Starita
    Howard Hughes Medical Institute, Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 110:E1263-72. 2013
    ..Our results highlight the general utility of high-throughput mutagenesis in delineating the molecular basis of enzyme activity.
  24. pmc Break-induced replication is highly inaccurate
    Angela Deem
    Department of Biology, School of Science, IUPUI, Indianapolis, Indiana, United States of America
    PLoS Biol 9:e1000594. 2011
    ..Here we employed a series of frameshift reporters to measure mutagenesis associated with BIR in Saccharomyces cerevisiae...
  25. pmc Vibrio cholerae triggers SOS and mutagenesis in response to a wide range of antibiotics: a route towards multiresistance
    Zeynep Baharoglu
    Institut Pasteur, Unité Plasticité du Génome Bactérien, Département Génomes et Génétique, 25 rue du Dr Roux, F 75015 Paris, France
    Antimicrob Agents Chemother 55:2438-41. 2011
    ..We show that unlike the situation with E. coli, all these antibiotics induce SOS in V. cholerae...
  26. pmc APOBEC3G contributes to HIV-1 variation through sublethal mutagenesis
    Holly A Sadler
    Institute for Molecular Virology, 18 242 Moos Tower, 515 Delaware St SE, University of Minnesota, Minneapolis, MN 55455, USA
    J Virol 84:7396-404. 2010
    ..cytosine deaminase activity that attacks the nascent viral cDNA during reverse transcription, causing lethal mutagenesis. It has been suggested, but not formally shown, that APOBEC3G can also induce sublethal mutagenesis, which ..
  27. ncbi Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
    Bastien Mangeat
    Department of Genetics and Microbiology, University of Geneva, 1211 Geneva 4, Switzerland
    Nature 424:99-103. 2003
    ..We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens...
  28. pmc Human quiescin-sulfhydryl oxidase, QSOX1: probing internal redox steps by mutagenesis
    Erin J Heckler
    Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA
    Biochemistry 47:4955-63. 2008
    ..The four other cysteine residues chosen for mutagenesis, C70, C73, C449, and C452, are all crucial for efficient oxidation of reduced RNase...
  29. pmc High efficiency mutagenesis, repair, and engineering of chromosomal DNA using single-stranded oligonucleotides
    H M Ellis
    Gene Regulation and Chromosome Biology Laboratory, Division of Basic Sciences, National Cancer Institute at Frederick, P.O. Box B, Frederick, MD 21702, USA
    Proc Natl Acad Sci U S A 98:6742-6. 2001
    ..Beta protein and ssDNA may prove generally applicable for repairing DNA in many organisms...
  30. pmc Efficient gene targeting in Drosophila by direct embryo injection with zinc-finger nucleases
    Kelly 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 ..
  31. pmc Retroviral elements and their hosts: insertional mutagenesis in the mouse germ line
    Irina 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...
  32. ncbi En passant mutagenesis: a two step markerless red recombination system
    B Karsten Tischer
    Institut fur Virologie, Freie Universitat Berlin, Berlin, Germany
    Methods Mol Biol 634:421-30. 2010
    ..In addition to RecA-based shuttle mutagenesis, Red recombination is commonly used for sequence modification...
  33. pmc Discovery of rare mutations in populations: TILLING by sequencing
    Helen Tsai
    Department of Plant Biology and Genome Center, University of California, Davis, California 95616, USA
    Plant Physiol 156:1257-68. 2011
    ..Discovery was robust both in rice and wheat using either bidimensional or tridimensional pooling schemes. The method compared favorably with other molecular and computational approaches, providing high sensitivity and specificity...
  34. ncbi ENU mutagenesis, a way forward to understand gene function
    Abraham Acevedo-Arozena
    MRC Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 0RD, United Kingdom
    Annu Rev Genomics Hum Genet 9:49-69. 2008
    ..N-ethyl-N-nitrosourea (ENU) mutagenesis has been widely used for both approaches to generate mouse mutants...
  35. ncbi The ClosTron: Mutagenesis in Clostridium refined and streamlined
    John 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. 2010
    The 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...
  36. ncbi Stress-induced mutagenesis in bacteria
    Ivana Bjedov
    INSERM U571, Faculte de Medecine Necker Enfants Malades, Université ParisV, 156 rue Vaugirard, 75730 ParisCedex 15, France
    Science 300:1404-9. 2003
    The evolutionary significance of stress-induced mutagenesis was evaluated by studying mutagenesis in aging colonies (MAC) of Escherichia coli natural isolates...
  37. pmc Estimating the per-base-pair mutation rate in the yeast Saccharomyces cerevisiae
    Gregory 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...
  38. ncbi Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution
    Sohrab P Shah
    Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
    Nature 461:809-13. 2009
    ..Taken together, our data show that single nucleotide mutational heterogeneity can be a property of low or intermediate grade primary breast cancers and that significant evolution can occur with disease progression...
  39. pmc Large-scale transposon mutagenesis of Mycoplasma pulmonis
    Christopher 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...
  40. ncbi High-throughput target-selected gene inactivation in zebrafish
    Ross N W Kettleborough
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
    Methods Cell Biol 104:121-7. 2011
    ..The efficiency of TILLING (Targeting Induced Local Legions IN Genomes) depends on the rate of mutagenesis in the library being screened, the amount of base pairs screened, and the ability to effectively identify and ..
  41. ncbi An enhanced system for unnatural amino acid mutagenesis in E. coli
    Travis S Young
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Mol Biol 395:361-74. 2010
    ..afforded increased plasmid stability compared with previously reported vectors for unnatural amino acid mutagenesis. To demonstrate the utility of this new system, we introduced 14 mutant aaRS into pEVOL and compared their ..
  42. ncbi Identification of virulence determinants in uropathogenic Proteus mirabilis using signature-tagged mutagenesis
    Stephanie D Himpsl
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Med Microbiol 57:1068-78. 2008
    ..cell-wall synthesis and metabolism, many of which have been identified using the technique of signature-tagged mutagenesis (STM)...
  43. pmc Targeted and random mutagenesis of Ehrlichia chaffeensis for the identification of genes required for in vivo infection
    Chuanmin Cheng
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA
    PLoS Pathog 9:e1003171. 2013
    ..Targeted mutagenesis at six genomic locations by homologous recombination and mobile group II intron-based methods led to the ..
  44. ncbi A highly active synthetic mammalian retrotransposon
    Jeffrey S Han
    Department of Molecular Biology and Genetics and High Throughput Biology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 429:314-8. 2004
    ..These synthetic retrotransposons are also the most highly active L1 elements known so far and have potential as practical tools for manipulating mammalian genomes...
  45. pmc Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis
    Mary 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.
  46. pmc SHPRH and HLTF act in a damage-specific manner to coordinate different forms of postreplication repair and prevent mutagenesis
    Jia Ren Lin
    Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA
    Mol Cell 42:237-49. 2011
    ..Postreplication repair (PRR) pathways play important roles in restarting stalled replication forks and regulating mutagenesis. In yeast, Rad5-mediated damage avoidance and Rad18-mediated translesion synthesis (TLS) are two forms of PRR...
  47. pmc In vivo mutagenesis reveals that OriL is essential for mitochondrial DNA replication
    Sjoerd Wanrooij
    Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P O Box 440, SE 405 30 Gothenburg, Sweden
    EMBO Rep 13:1130-7. 2012
    ..We here use in vivo saturation mutagenesis to demonstrate that OriL is essential for mtDNA maintenance in the mouse...
  48. ncbi A practical summary of site-specific recombination, conditional mutagenesis, and tamoxifen induction of CreERT2
    Konstantinos Anastassiadis
    Center for Regenerative Therapy, Technische Universitaet Dresden, Dresden, Germany
    Methods Enzymol 477:109-23. 2010
    ..Cre recombinase is vital for conditional mutagenesis, including for temporal mutagenesis via tamoxifen induction of recombinase-estrogen receptor fusion proteins...
  49. pmc Massively parallel sequencing of the mouse exome to accurately identify rare, induced mutations: an immediate source for thousands of new mouse models
    T D Andrews
    Immunogenomics Laboratory, Australian National University, GPO Box 334, Canberra City, Australian Capital Territory, 2601, Australia
    Open Biol 2:120061. 2012
    ..This approach transforms genetic screens in mice, establishes a general strategy for analysing rare DNA variants and opens up a large new source for experimental models of human disease...
  50. ncbi The mechanisms of UV mutagenesis
    Hironobu Ikehata
    Division of Genome and Radiation Biology, Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai, Japan
    J Radiat Res 52:115-25. 2011
    ..In contrast, it has been demonstrated that UVA exclusively induces the solar-UV signature mutations in vivo through CPD formation...
  51. pmc Genome-wide mutagenesis of Xanthomonas axonopodis pv. citri reveals novel genetic determinants and regulation mechanisms of biofilm formation
    Jinyun Li
    Department of Microbiology and Cell Science, Citrus Research and Education Center, University of Florida, Lake Alfred, Florida, United States of America
    PLoS ONE 6:e21804. 2011
    ..The report provides significant new information about the genetic determinants and regulatory mechanism of biofilm formation...
  52. ncbi Phenotypic characterization of a new Grin1 mutant mouse generated by ENU mutagenesis
    Tamio Furuse
    Technology and Development Team for Mouse Phenotype Analysis Japan Mouse Clinic, RIKEN BioResource Center, 3 1 1 Koyadai, Tsukuba, Ibaraki 305 0074, Japan
    Eur J Neurosci 31:1281-91. 2010
    In the RIKEN large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis project we screened mice with a dominant mutation that exhibited abnormal behavior in the open-field test, passive avoidance test and home-cage activity test...
  53. pmc Genetic steps of mammalian homologous repair with distinct mutagenic consequences
    Jeremy M Stark
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Mol Cell Biol 24:9305-16. 2004
    ..These results imply that the proper genetic interplay of repair factors is essential to limit the mutagenic potential of DSB repair...
  54. ncbi Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E
    Christian Sinzger
    Institut fur Medizinische Virologie, Eberhard Karls Universitat, Tubingen, Germany
    J Gen Virol 89:359-68. 2008
    ..Removal of this insertion by markerless mutagenesis restored the highly endotheliotropic phenotype, indicating that the loss of endothelial cell tropism was caused ..
  55. ncbi Gene targeting by homologous recombination in Drosophila
    Y S Rong
    Department of Biology, University of Utah, Salt Lake City, UT 84112, USA
    Science 288:2013-8. 2000
    ..A method is described that enables analogous manipulations of the Drosophila genome. This technique may also be applicable to other organisms for which gene-targeting procedures do not yet exist...
  56. pmc Identification and characterization of Aspergillus nidulans mutants defective in cytokinesis
    S D Harris
    Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907 1392
    Genetics 136:517-32. 1994
    ..This class of mutants suggests the existence of a regulatory mechanism in A. nidulans that ensures the continuation of nuclear division following the initiation of cytokinesis...
  57. pmc Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I
    Nayun Kim
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Science 332:1561-4. 2011
    ..The reported studies extend the role of Top1 to include the processing of rNMPs in genomic DNA into irreversible single-strand breaks, an activity that can have distinct mutagenic consequences and may be relevant to human disease...
  58. ncbi Mouse phenotyping
    Helmut Fuchs
    Institute of Experimental Genetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 München Neuherberg, Germany
    Methods 53:120-35. 2011
    ..Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in ..
  59. ncbi Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor
    Y Uehara
    Institute for Liver Research, Kansai Medical University, Moriguchi, Osaka, Japan
    Nature 373:702-5. 1995
    ..These findings suggest that HGF/SF is an essential mediator of allantoic mesenchyme-trophoblastic epithelia interaction required for placental organogenesis...
  60. pmc Chromosomal transposition of PiggyBac in mouse embryonic stem cells
    Wei 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...
  61. pmc Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition
    Oliver Weigert
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Exp Med 209:259-73. 2012
    ..Thus, HSP90 is a promising therapeutic target in JAK2-driven cancers, including those with genetic resistance to JAK enzymatic inhibitors...
  62. pmc A stabilized respiratory syncytial virus reverse genetics system amenable to recombination-mediated mutagenesis
    Anne L Hotard
    Department of Pediatrics, Emory University, Atlanta, GA 30322, USA
    Virology 434:129-36. 2012
    We describe the first example of combining bacterial artificial chromosome (BAC) recombination-mediated mutagenesis with reverse genetics for a negative strand RNA virus...
  63. pmc A four-subunit DNA polymerase ζ complex containing Pol δ accessory subunits is essential for PCNA-mediated mutagenesis
    Alena V Makarova
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    Nucleic Acids Res 40:11618-26. 2012
    DNA polymerase ζ (Pol ζ) plays a key role in DNA translesion synthesis (TLS) and mutagenesis in eukaryotes...
  64. pmc Mutagenesis of Burkholderia pseudomallei with Tn5-OT182: isolation of motility mutants and molecular characterization of the flagellin structural gene
    D DeShazer
    Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Alberta, Canada
    J Bacteriol 179:2116-25. 1997
    ..In this report, we describe the mutagenesis of B. pseudomallei with the transposon Tn5-OT182. B...
  65. pmc T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro
    Tatiana Baranovich
    Department of Infectious Diseases, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    J Virol 87:3741-51. 2013
    ..that T-705 induces a high rate of mutation that generates a nonviable viral phenotype and that lethal mutagenesis is a key antiviral mechanism of T-705...
  66. pmc Genome instability due to ribonucleotide incorporation into DNA
    Stephanie A Nick McElhinny
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
    Nat Chem Biol 6:774-81. 2010
  67. pmc Systematic mutagenesis of α-synuclein reveals distinct sequence requirements for physiological and pathological activities
    Jacqueline Burré
    Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305 5453, USA
    J Neurosci 32:15227-42. 2012
  68. pmc Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products
    M N Seaman
    Division of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla 92093 0668, USA
    J Cell Biol 137:79-92. 1997
  69. pmc Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint
    Dinesh 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...
  70. pmc Critical amino acids in Escherichia coli UmuC responsible for sugar discrimination and base-substitution fidelity
    Alexandra Vaisman
    Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 3371, USA
    Nucleic Acids Res 40:6144-57. 2012
    The active form of Escherichia coli DNA polymerase V responsible for damage-induced mutagenesis is a multiprotein complex (UmuD'(2)C-RecA-ATP), called pol V Mut...
  71. pmc A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels
    Jason 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...
  72. ncbi Fractionation mutagenesis and similar consequences of mechanisms removing dispensable or less-expressed DNA in plants
    Michael Freeling
    Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA
    Curr Opin Plant Biol 15:131-9. 2012
    ..Regulatory DNA deletion following polyploidy combined with abundant RNA-seq expression datasets are being used to generate testable hypothesizes regarding the function of specific cis-regulatory sequences...
  73. pmc DNA polymerase δ and ζ switch by sharing accessory subunits of DNA polymerase δ
    Andrey G Baranovskiy
    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
    J Biol Chem 287:17281-7. 2012
    ..Amino acid changes in Pol ζ that prevent the assembly of the [4Fe-4S] cluster abrogate Pol ζ function in UV mutagenesis. On the basis of these data, we propose that Pol switches at replication-blocking lesions occur by the exchange ..
  74. ncbi Exportin 1 (Crm1p) is an essential nuclear export factor
    K Stade
    Department of Biochemistry and Biophysics, University of California at San Francisco, 94143 0414, USA
    Cell 90:1041-50. 1997
    ..cerevisiae. The presented data are consistent with the conclusion that Crm1p is a carrier for the NES-mediated protein export pathway. We propose CRM1 be renamed exportin 1 (XPO1)...
  75. pmc Concomitant lethal mutagenesis of human immunodeficiency virus type 1
    Michael J Dapp
    Institute for Molecular Virology, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, USA
    J Mol Biol 419:158-70. 2012
    ..One such approach, termed lethal mutagenesis, is directed at targeting the virus population structure for extinction or error catastrophe...
  76. ncbi Knowledge-based computational mutagenesis for predicting the disease potential of human non-synonymous single nucleotide polymorphisms
    Majid 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 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...
  77. pmc Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients
    Steven 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...
  78. ncbi Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis
    Jesse 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. 2003
    In 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 ..
  79. ncbi Repair and genetic consequences of endogenous DNA base damage in mammalian cells
    Deborah E Barnes
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Annu Rev Genet 38:445-76. 2004
    ..The genetic instability characteristic of cancer cells may be due, in part, to mutations in genes whose products normally function to ensure DNA integrity...
  80. ncbi A general system for generating unlabelled gene replacements in bacterial chromosomes
    K Leenhouts
    Department of Genetics, University of Groningen, Haren, The Netherlands
    Mol Gen Genet 253:217-24. 1996
    ..A feasibility study was performed using Lactococcus lactis and Bacillus subtilis as model organisms. The results indicate that the method should be applicable to any non-essential gene in numerous bacterial species...
  81. ncbi Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation
    A M Lindroth
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Science 292:2077-80. 2001
    ..They also show reactivated expression of endogenous retrotransposon sequences. These results show that a non-CpG DNA methyltransferase is responsible for maintaining epigenetic gene silencing...
  82. pmc PCNA ubiquitination is important, but not essential for translesion DNA synthesis in mammalian cells
    Ayal Hendel
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    PLoS Genet 7:e1002262. 2011
    ..specialized low-fidelity DNA polymerases bypass replication-blocking lesions, and it is usually associated with mutagenesis. In Saccharomyces cerevisiae a key event in TLS is the monoubiquitination of PCNA, which enables recruitment of ..
  83. pmc MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence
    Scott E Converse
    Department of Microbiology and Immunology, G W Hooper Foundation, University of California, San Francisco 94143, USA
    Proc Natl Acad Sci U S A 100:6121-6. 2003
  84. pmc Spontaneous mutagenesis is enhanced in Apex heterozygous mice
    Jessica Huamani
    Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 78229 3900, USA
    Mol Cell Biol 24:8145-53. 2004
    ..These data indicate that diminution of AP endonuclease has a significant effect on spontaneous mutagenesis in somatic and germ line cells.
  85. ncbi A switch from high-fidelity to error-prone DNA double-strand break repair underlies stress-induced mutation
    Rebecca G Ponder
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell 19:791-804. 2005
    ..We provide evidence that the molecular basis for stress-induced mutagenesis in an E. coli model is error-prone DNA double-strand break repair (DSBR)...
  86. pmc Generation of a nicking enzyme that stimulates site-specific gene conversion from the I-AniI LAGLIDADG homing endonuclease
    Audrey 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.
  87. ncbi Interactions in the error-prone postreplication repair proteins hREV1, hREV3, and hREV7
    Y Murakumo
    Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai Cho, Showa Ku, Nagoya 466 8550, Japan
    J Biol Chem 276:35644-51. 2001
    ..hREV1) and REV3 (hREV3) genes were identified, and their products were revealed to be involved in UV-induced mutagenesis, as observed for their yeast counterparts...
  88. ncbi Oxidative damage to DNA: formation, measurement and biochemical features
    Jean 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...
  89. pmc Efficient genome-wide mutagenesis of zebrafish genes by retroviral insertions
    Dongmei Wang
    Key Laboratory of Cell Proliferation and Differentiation, Center of Developmental Biology and Genetics, College of Life Sciences, Peking University, Ministry of Education, Beijing 100871, China
    Proc Natl Acad Sci U S A 104:12428-33. 2007
    ..Combining this increase in efficiency with cryopreservation of sperm samples from the F(1) fish, it is now possible to create a stable resource that contains mutations in every known zebrafish gene...
  90. ncbi Iterative saturation mutagenesis (ISM) for rapid directed evolution of functional enzymes
    Manfred T Reetz
    Max Planck Institut fur Kohlenforschung, Kaiser Wilhelm Platz 1, 45470 Mulheim Ruhr, Germany
    Nat Protoc 2:891-903. 2007
    Iterative saturation mutagenesis (ISM) is a new and efficient method for the directed evolution of functional enzymes. It reduces the necessary molecular biological work and the screening effort drastically...
  91. pmc Chemical biology of mutagenesis and DNA repair: cellular responses to DNA alkylation
    Nidhi Shrivastav
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Carcinogenesis 31:59-70. 2010
    ..Here, we describe the respective contributions of specific DNA lesions to the biological effects of low molecular weight alkylating agents...
  92. pmc Systematic dissection and trajectory-scanning mutagenesis of the molecular interface that ensures specificity of two-component signaling pathways
    Emily J Capra
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
    PLoS Genet 6:e1001220. 2010
    ..To explore how a relatively small set of residues can dictate partner selectivity, we combined alanine-scanning mutagenesis with an approach we call trajectory-scanning mutagenesis, in which all mutational intermediates between the ..
  93. pmc Allosteric features of KCNQ1 gating revealed by alanine scanning mutagenesis
    Li Juan Ma
    Institut für Neurale Signalverarbeitung, Zentrum für Molekulare Neurobiologie, Universitat Hamburg, Hamburg, Germany
    Biophys J 100:885-94. 2011
    ..We applied alanine scanning mutagenesis to the S4-S5 linker and pore region and followed the regularities of gating perturbations in KCNQ1...
  94. pmc Targeted mutagenesis of duplicated genes in soybean with zinc-finger nucleases
    Shaun J Curtin
    Department of Agronomy and Plant Genetics, University of Minnesota, St Paul, Minnesota 55108, USA
    Plant Physiol 156:466-73. 2011
    We performed targeted mutagenesis of a transgene and nine endogenous soybean (Glycine max) genes using zinc-finger nucleases (ZFNs)...
  95. ncbi An evaluation of Poisson-Boltzmann electrostatic free energy calculations through comparison with experimental mutagenesis data
    Ronald D Gorham
    Department of Bioengineering, University of California, Riverside, CA 92521, USA
    Biopolymers 95:746-54. 2011
    ..Using experimental or theoretical alanine-scanning mutagenesis, it is possible to elucidate the contribution of individual ionizable amino acids to protein association...
  96. pmc The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA
    Hui Zhang
    The Dorrance H Hamilton Laboratories, Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Nature 424:94-8. 2003
    ..Importantly, the accumulation of CEM15-mediated non-lethal hypermutation in the replicating viral genome could potently contribute to the genetic variation of primate lentiviral populations...
  97. ncbi Tight steric closure at the intracellular activation gate of a voltage-gated K(+) channel
    D del Camino
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
    Neuron 32:649-56. 2001
    ..Either these Kv channels have a broader inner entrance than seen in the KcsA crystal, even in the closed state, or the region is highly flexible (but nevertheless remains very securely closed nearby)...
  98. ncbi An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda
    Ivana Barbaric
    MRC Mammalian Genetics Unit, Harwell
    Physiol Genomics 32:311-21. 2008
    ..As an effort toward identifying novel genes involved in regulation of bone mass, N-ethyl-N-nitrosourea (ENU) mutagenesis in mice has been utilized...
  99. ncbi Unravelling UVA-induced mutagenesis
    Evelyne Sage
    Institut Curie, CNRS UMR3348, Universite de Paris Sud XI, F 91405, Orsay Cedex, France
    Photochem Photobiol Sci 11:74-80. 2012
    ..This may help unravel the role of UVA in the various steps of photocarcinogenesis. The connection to photocarcinogenesis is more extensively discussed by other authors in this issue...
  100. ncbi ENU-based gene-driven mutagenesis in the mouse: a next-generation gene-targeting system
    Yoichi Gondo
    Mutagenesis and Genomics Team, RIKEN BioResource Center, Ibaraki, Japan
    Exp Anim 59:537-48. 2010
    As a new mouse mutant resource, the RIKEN ENU-based gene-driven mutagenesis system in the mouse has been available to the research community since 2002...
  101. pmc Cre-lox-based system for multiple gene deletions and selectable-marker removal in Lactobacillus plantarum
    Jolanda 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 ..

Research Grants79

  1. Pilot and definitive studies to evaluate Insertional Mutagenesis
    LU TAYLOR; Fiscal Year: 2012
    ..FDA-NTP Studies of Insertional Mutagenesis - Pilot Study: 12-week pilot study has been awarded to the lab to develop and validate preclinical model for ..
  2. Studies to Evaluate the Toxicological Potential of Test Articles
    LU TAYLOR; Fiscal Year: 2010
    ..FDA-NTP Studies of Insertional Mutagenesis - Pilot Study: 12-week pilot study has been awarded to the lab to develop and validate preclinical model for ..
  3. DNA Damage and Response in the Bladder Microenvironment.
    Bradley P Dixon; Fiscal Year: 2013
    ..of DNA damage in susceptible tissues such as the gastrointestinal portion of an augmented bladder, leading to mutagenesis and ultimately carcinogenesis...
  4. Role of Polyamines in MYCN-Amplified Neuroblastoma
    ANDRE BACHMANN; Fiscal Year: 2009
    ..RNA half-life studies, Western blot, yeast two-hybrid, co-immunoprecipitation, GST-pull down, site-directed mutagenesis, DNA cloning, confocal laser microscopy, enzyme and in vitro kinase assays, flow cytometry, and HPLC...
  5. Investigating Mechanism of Intracellular Rotational Transport with Optical T
    Jeffrey N Anker; Fiscal Year: 2012
    ..and associated overproduction of reactive oxygen species further oxidize RNA/DNA/proteins, leading to fibrosis, mutagenesis and lung cancer...
    Pi Wan Cheng; Fiscal Year: 2010
    ..of C2GnT-M by X-ray crystallography and then confirm the amino acids involved in catalysis by site-directed mutagenesis followed by measurement of enzyme activities using core 1, core 3, and blood group i disaccharide acceptors and ..
  7. Role and Regulation of INrf2
    ANIL KUMAR JAISWAL; Fiscal Year: 2013
    ..Sitedirected mutagenesis along with transfection and reporter assays, immunoprecipitation and Western analysis will be used to achieve ..
  8. Role of Diabetes in Development of Renal Cell Carcinoma
    SAMY LEWIZ HABIB; Fiscal Year: 2013
    ..8-OxodG enhances mutagenesis and predisposes the kidney and other organs to cancer...
    DHAN V KALVAKOLANU; Fiscal Year: 2013
    ..relevance of these factors to DAPK1 and autophagy using RNAi, knockout mice, protein-interactions, ChIP assays, mutagenesis and transcriptional analyses...
  10. Fatty acid related regulation of enteric infectious disease
    FREDRICK JON KULL; Fiscal Year: 2012
    ..using electrophoretic mobility shift assays (EMSAs), an NMR-based ligand binding assay, and site directed mutagenesis. Preliminary analysis has indicated that a number of pathogenic bacteria, including several types of ..
  11. Novel DNA-Launched Attenuated Vaccine for VEE Virus
    PETER M PUSHKO; Fiscal Year: 2012
    ..In Specific Aim I, we will apply innovative "silent mutagenesis" method to introduce additional genetic changes into the prototype TC-83 i-DNA in order to secure attenuated ..
  12. FOXP3-microRNA146-NFkB Axis in Tumor Suppression
    Lizhong Wang; Fiscal Year: 2013
    ..electrophoretic mobility shift assay and luciferase reporter assays as well as site-directed mutagenesis to identify the functional forkhead motif...
  13. Microsomal Cytochromes P450 and their Interactions with their Redox Partners
    Lucy A Waskell; Fiscal Year: 2013
    ..Experimental techniques, including site-directed mutagenesis, rapid quenching of cyt P450 activity by chemical means, and freezing, HPLC-mass spectrometry, and quantum ..
  14. Novel Therapy for Preeclampsia
    James W Larrick; Fiscal Year: 2012
    ..Affinity maturation, in combination with targeted in vitro mutagenesis of specific amino acids known to modify specificity of the binding site for digoxin, will yield multipe clones...
  15. DNA Repair Deficiency Associated with Obesity and the Metabolic Syndrome
    R Stephen Lloyd; Fiscal Year: 2013
    ..These analyses will be complemented by examining the role of NEIL1 in the modulation of survival, mutagenesis, and mitochondrial function in response to oxidative or nitric oxide stress conditions...
  16. Folate Status, Genomic Uracil, and the Balance of Base Excision Repair Activity
    Michael D Wyatt; Fiscal Year: 2011
    ..In other words, MBD4 is thought to act as a tumor suppressor by preventing CpG to TpG mutagenesis caused by deamination of cytosine or 5-methylcytosine. Thus, several questions arise...
  17. Ferritin: Protein/mRNA/DNA in Fe/O Regulation/Metabolism
    ELIZABETH C contact THEIL; Fiscal Year: 2010
    ..fluorescence MCD/CD, NMR spectroscopies, and X-ray crystallography), Molecular Biology (in vitro translation, mutagenesis, protein expression, EMSA, DNA-5mC analysis), and Cell Biology (RT-PCR, immunoblotting)...
  18. Regulation of Genomic and Epigenomic Stability at CpG Sites
    Alfonso Bellacosa; Fiscal Year: 2013
    ..both the genomic and epigenomic stability of CpG sites, in order to ward off against developmental defects, mutagenesis and tumorigenesis...
  19. Retroviral Vector-mediated Liver Gene Therapy for MPS I
    Katherine P Ponder; Fiscal Year: 2013
    ..Although no tumors developed in mice or dogs with this approach, the risk of insertional mutagenesis with an LTR-intact vector is a concern...
  20. Colitis Induced by immune responses to luminal bacteria-mouse
    Ryan B Sartor; Fiscal Year: 2012
    ..coli K12, and identifying NC101 genes that determine epithelial invasion and translocation by signature tagged mutagenesis. B. In vitro studies. Does 1) intracellular bacterial survival and 2) secretion of superoxide by E...
  21. Neuropilin and semaphorin, anti-angiogenesis activities and mechanisms
    Michael Klagsbrun; Fiscal Year: 2009
    ..Alteration of the NRP2 B domain structure by site-directed mutagenesis improved the affinity of the B-NRP2 mutants to VEGF by almost one log but had no effect on SEMA3F affinity...
  22. Neonatal Chemoselection Following Ex Vivo Gene Transfer For Hereditary Disorders
    KARIN L GAENSLER; Fiscal Year: 2012
    ..Potential risks of transplantation of such genetically modified allogeneic HSC include GVHD and insertional mutagenesis resulting in uncontrolled clonal proliferation...
  23. Potentiation of Glycine Receptors by Ethanol
    LUIS GERARDO AGUAYO; Fiscal Year: 2010
    ..the intracellular sites responsible for G protein activation and GlyR sensitivity to ethanol by using receptor mutagenesis, kinetic analysis of GTP binding to G proteins, heterologous expression of G protein subunits, patch-clamp and ..
  24. Regulation of factor VIII Levels and Activity by Members of LDL Receptor Family
    Dudley K Strickland; Fiscal Year: 2013
    ..This will be accomplished by site-directed mutagenesis of key regions on the fVIII molecule that contribute to LRP-, LDLR- and HSPG-binding...
  25. Nitric Oxide Signaling with Heme Proteins
    William R Montfort; Fiscal Year: 2012
    ..Experiments involving X-ray crystallography, electron microscopy and mutagenesis are proposed. Specific Aim 2 is to understand mechanism in the allosteric regulation of sGC...
    Zbigniew Darzynkiewicz; Fiscal Year: 2013
    ..These assays will find utility in studies of DNA damage, DNA repair, carcinogenesis/mutagenesis, apoptosis, and in identifying the mechanism of action of antitumor drugs...
  27. Delineation of the molecular mechanisms underlying group A Streptococcus virulenc
    Paul Sumby; Fiscal Year: 2013
    ..To facilitate investigation of FASX regulatory targets and mechanism/s of action we will perform site-directed mutagenesis on fasX...
  28. A Cis-regulatory Model for Neural Border Induction
    Daniel Meulemans Medeiros; Fiscal Year: 2013
    ..The proposed work will test this model using mRNA injections, mutagenesis, and chromatin immunoprecipitation (ChIP)...
  29. Regulation of the Endothelial Citrulline-Nitric Oxide Cycle
    Duane C Eichler; Fiscal Year: 2010
    ..and NO assays;4) fluorescence microscopy;5) real time PCR and western blotting;and 6) promoter analysis using mutagenesis, luciferase assays and EMSA studies...
    Frances M Brodsky; Fiscal Year: 2013
    ..The experimental approaches to these studies include protein crystallography and structure-based mutagenesis, RNA interference, membrane traffic and migration assays, and gene targeting strategies to produce animals that ..
  31. Varicella zoster virus: molecular controls of cell fusion-dependent pathogenesis
    Ann Arvin; Fiscal Year: 2013
    ..Lysine mutagenesis studies will be performed to assess the effects of acetylation and ubiquitination posttranslational ..
    William M Nauseef; Fiscal Year: 2013
    ..Using transposon mutagenesis in F...
  33. Fnip1 Function in Lymphocyte Development, Activation and Metabolism
    Brian M Iritani; Fiscal Year: 2013
    ..We identified an innovative new strain of mice lacking Fnip1 in a chemical mutagenesis screen, based on the complete absence of B lymphocytes in peripheral blood...
    Richard Armstrong; Fiscal Year: 2009
    ..This will be accomplished by;(i) rational mutagenesis and directed evolution of FosA and FosX activities from a promiscuous progenitor encoded in the genome of ..
  35. ANP Receptor: Molecular approach of signaling mechanisms
    Kailash N Pandey; Fiscal Year: 2013
    ..of the receptor will be used to elucidate those receptor areas that can be further analyzed by site- directed mutagenesis in transfected cells in vitro and transgenic mouse models in vivo to learn what structural components are ..
    Shiou Chuan Tsai; Fiscal Year: 2010
    ..binding pockets of AccD4, AccD5 and AccD6, and define the substrate/inhibitor binding residues by site-directed mutagenesis: (3.1) Systematically mutate AccD5 residue 437 to evaluate its importance for substrate specificity. (3...
  37. Identifying Key Structural Elements in the Activation of the Arp2/3 Complex
    Patricia A Khuu; Fiscal Year: 2013
    ..We will use mutagenic primers for site-directed mutagenesis, along with homologous recombination, gene knock-out and gene replacement, to create mutant strains...
  38. Biosynthesis of Microbial Isoprenoids
    David E Cane; Fiscal Year: 2013
    ..the protein structural basis for catalysis and product specificity using a combination of site-directed mutagenesis and protein crystallography...
  39. Tick-Mammal Interface of Human Granulocytic Anaplasmosis
    ..By specifically disrupting Ap gene expression using insertional mutagenesis the essential processes which Ap performs to infect its different hosts can be sorted into common an host-..
  40. X-ray Studies of Sugar-Modifying Enzymes
    Hazel Holden; Fiscal Year: 2013
    ..array of intriguing enzymes that will be investigated in this proposal by X-ray crystallography, site-directed mutagenesis experiments, and kinetic analyses...
  41. Biosynthetic Protein Models of Heme-copper Oxidases and Nitric Oxide Reductases
    Yi Lu; Fiscal Year: 2013
    ..CuBMb and FeBMb, respectively), as demonstrated by both spectroscopy and X-ray crystallography, site-directed mutagenesis and expressed protein ligation (EPL) will be employed to introduce natural or unnatural amino acids into the ..
  42. Regulation of the Expression of G[alpha]i2 by Reactive Oxygen Species
    Ifeanyi J Arinze; Fiscal Year: 2012 fluorescence imaging of transfected green fluorescence protein (GFP)-tagged Nrf2, and by site-directed mutagenesis to assess the functionality of novel nuclear localization sequences in the protein...
  43. Transcriptional regulation of proteinuria
    SUMANT SINGH CHUGH; Fiscal Year: 2011
    ..ZHX3 to the COL4A3 promoter will be studied by a combination of chromatin immunoprecipitation and site directed mutagenesis. Next, the influence of ZHX3 and interacting partners on the promoter activity of selected genes will be ..
  44. Thrombospondin 4 A1
    JOHN W LAWLER; Fiscal Year: 2010
    ..basis for the interaction of COMP with collagens, integrins, and glycosaminoglycans (GAGs) by site-directed mutagenesis within the context of the intact molecule and the recombinant signature domain...
  45. Stem cell mutagenesis mediated by age and niche
    VIVIENNE ILONA REBEL; Fiscal Year: 2011
    ..the different tissues is maintained during aging is limited largely to analyses of DNA damage, DNA repair, and mutagenesis in differentiated cells and tissues...
  46. Influence of Heme on Hepatic Cytochrome P450 Turnover
    Maria Almira Correia; Fiscal Year: 2013
    ..Such elucidation will rely on approaches such as site-directed mutagenesis, lentiviral shRNA interference, immunoaffinity capture and proteomic analyses...
  47. Dopamine Transporter Structure and Function
    Christopher K Surratt; Fiscal Year: 2010
    ..creation of a LeuT-based 3-D DAT model and use of the model to identify and characterize, via DAT site-directed mutagenesis/pharmacology and crosslinking of novel DAT ligands, the DAT residues key to ligand recognition...
  48. Building Mouse Models of Metabolic Syndrome
    Karen L Svenson; Fiscal Year: 2013
    ..carrying single gene mutations causing metabolic syndrome-related traits has been developed in a large-scale mutagenesis program at The Jackson Laboratory...
    Maria Almira Correia; Fiscal Year: 2013
    ..Thus our first specific aim is to test this hypothesis by site-directed mutagenesis of the relevant D/E and S/T residues in each cluster along with a state-of-the-art proteomic approach to ..
  50. Creation of hyperactive transposons for mutagenesis in rodents
    Eric M Ostertag; Fiscal Year: 2011
    ..PUBLIC HEALTH RELEVANCE: In the application "Creation of hyperactive transposases for mutagenesis in rodents," we are seeking Phase II funding to use the novel transposases we created to generate new models of ..
  51. Analysis of the tumor suppressor gene Tsc1 in motor neuron patterning
    Onanong Chivatakarn; Fiscal Year: 2013
    ..From the ENU mutagenesis screen, nine independent mutants were identified and their corresponding genes were cloned...
    Jeffrey A Simon; Fiscal Year: 2012
    ..The methods will include loss-of-function and over-expression studies, site-directed mutagenesis, transgene manipulation, chromatin immuneprecipitation, enzyme assays, protein purification and chromosome ..
  53. Gene Therapy for Retinitis Pigmentosa
    Rajendra Kumar-Singh; Fiscal Year: 2012
    ..recently shown to cause hepatocellular carcinoma at the alarmingly high rate of 56% in animals by insertional mutagenesis. Hence, there is a need for gene therapy vectors that persist episomally...
    JAMES CARLTON GARRISON; Fiscal Year: 2010
    ..Lipin is phosphorylated in response to insulin. In AIM 1 a plan involving peptide mapping, site directed mutagenesis, and mass spectrometry is presented to determine the sites of phosphorylation...
  55. Melanopsin Signal Transduction Studied by FTIR Spectroscopy
    Kenneth J Rothschild; Fiscal Year: 2012
    ..advanced FTIR difference techniques, many developed in our laboratory, in conjunction with site-directed mutagenesis and isotope labeling...
  56. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2013
    ..We will test this hypothesis by manipulating through mutagenesis of these residues the selectivity of binding and permeability in order to alter the substrate specificity of ..
  57. Determinants of Disease Expression in Arrhythmogenic Cardiomyopathy
    Jeffrey E Saffitz; Fiscal Year: 2010
    ..Well established, highly productive methods for mutagenesis and genetic screening or small molecule screening can be applied to fish embryos to identify in an unbiased, ..
  58. The role of human DNA polymerase eta in the mutagenic response to oxidative stres
    SCOTT DAVID MCCULLOCH; Fiscal Year: 2013
    ..A similar logic has been proposed for the suppression of mutagenesis during pol 7 dependent bypass of 8-oxo-dG...
  59. Generation of Site-Specific Recombinase-Expressing Transgenic Rats using an Enhan
    Eric M Ostertag; Fiscal Year: 2011
    ..While in vitro gene trap mutagenesis is useful for gene discovery, a rapid and efficient in vivo method is preferable for two key reasons: 1) an in ..
  60. The role fo the TPP1 peotein in telomerase function and cancer cell survival
    Jayakrishnan Nandakumar; Fiscal Year: 2013
    ..structural elements in human TPP1 that lead to telomerase processivity stimulation using a site-directed mutagenesis screen, looking for separation-of-function mutants defective specifically in telomerase stimulation in vitro ..
  61. Novel Catalases and their Products
    Alan R Brash; Fiscal Year: 2013
    ..We also propose to change the AOS activity of these enzymes by site-direct mutagenesis of active site amino acids, a hypothesis supported by the array of products of CYP74 relatives of the P450 AOS...
  62. Novel High Affinity and Long-Acting Bovine FSH Analogs for Veterinary Superovulat
    BRUCE DALE WEINTRAUB; Fiscal Year: 2012
    ..novel high affinity recombinant bFSH superagonist analogs by minimal 4-5 arginine and/or lysine site-directed mutagenesis to produce a more potent and efficacious molecule with possible delayed absorption to increase duration of ..
    Chang An Yu; Fiscal Year: 2009
    ..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 ..
    CAROLE MENDELSON; Fiscal Year: 2007
    ..In deletion mapping and mutagenesis studies, we have[unreadable] found that basal and cAMP induction of rabbit and human SP-A promoter[unreadable] ..
  65. Monoamine Transporter Structure-Function Studies
    CHRISTOPHER 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...
  66. Genetic Basis of Myeloid Neoplasia--Mutagenesis Screens
    A 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 ..
  67. Genetic analysis of Cryptococcus neoformans virulence
    Joseph Heitman; Fiscal Year: 2009
    ..We propose to broadly apply Insertional mutagenesis to identify genes encoding virulence attributes necessary for infection. C...
    Robert Fowler; Fiscal Year: 1991
    ..superoxide radical, hydrogen peroxide and hydroxyl radical, are thought to be possible causative agents in mutagenesis, carcinogenesis and aging...
  69. Creation of hyperactive transposons for mutagenesis in rodents
    Eric Ostertag; Fiscal Year: 2009
    This project aims to rapidly produce rat mutants through a transposon-based method of mutagenesis. The rat is a favored model for many types of human disease for which mice are not suitable...
    Christopher Lawrence; Fiscal Year: 1999
    ..Christopher Lawrence proposes to continue a long-term study on the mechanism of DNA-damage induced mutagenesis in S. cerevisiae...
    KENDRIC SMITH; Fiscal Year: 1990
    One important finding from our studies on ionizing radiation mutagenesis (IRM). In Escherichia coli is that IRM is not uniformly dependent on the umuDC genes as is the case for UV radiation mutagenesis...
  72. Environmental Mutagen Society 2011 Annual Meeting
    CATHERINE G B KLEIN; Fiscal Year: 2011
    ..Society (EMS) is the primary scientific society fostering research on the basic mechanisms of DNA repair and mutagenesis and application of this knowledge to understanding human health effects from exposure to environmental toxins...
    Norman Drinkwater; Fiscal Year: 1992
    ..basis for carcinogen-induced mutations, recombinant DNA shuttle vectors were developed for analysis of mutagenesis in human lymphoblastoid cells...
    William Taylor; Fiscal Year: 1990
    ..find out which of the gamma-ray induced lesions in DNA are responsible for the biological effects; lethality, mutagenesis and chromosomal rearrangements...
  75. L1 retrotransposon-based mutagenesis for rat models of human diseases
    Eric Ostertag; Fiscal Year: 2009
    ..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 ..
    Stephen Crews; Fiscal Year: 2000
    ..Mutations will be generated following standard genetic screens, including an EMS mutagenesis (using a deficiency shown to uncover the Darnt gene) and a P-element transposition mutagenesis...
  77. Zebrafish ES cell lines for targeted mutagenesis
    Paul 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 ..
    THOMAS GRIFFITHS; Fiscal Year: 1991
    The project's long-term objectives are to help elucidate the molecular processes involved in carcinogenesis and mutagenesis. Specific aims relate to how the DNA lesions are handled in various eukaryotic cells...
    J 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 ..