recombinases

Summary

Summary: A broad category of enzymes that are involved in the process of GENETIC RECOMBINATION.

Top Publications

  1. pmc Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases
    Samira Fekairi
    Genome Instability and Carcinogenesis UPR3081 CNRS, Conventionné par l Université d Aix Marseille 2, IGC, IMM 31 chemin Joseph Aiguier, 13402 Marseille, France
    Cell 138:78-89. 2009
  2. pmc Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair
    Jennifer M Svendsen
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 138:63-77. 2009
  3. ncbi SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype
    Chantal Stoepker
    Department of Clinical Genetics, Vrije Universiteit VU Medical Center, Amsterdam, The Netherlands
    Nat Genet 43:138-41. 2011
  4. ncbi Talking about a revolution: The impact of site-specific recombinases on genetic analyses in mice
    Catherine S Branda
    Harvard Medical School, Department of Genetics, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Dev Cell 6:7-28. 2004
  5. pmc Chimeric TALE recombinases with programmable DNA sequence specificity
    Andrew C Mercer
    The Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Nucleic Acids Res 40:11163-72. 2012
  6. pmc Mutations of the SLX4 gene in Fanconi anemia
    Yonghwan Kim
    Laboratory of Genome Maintenance, The Rockefeller University, New York, New York, USA
    Nat Genet 43:142-6. 2011
  7. ncbi Mechanisms of site-specific recombination
    Nigel D F Grindley
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114, USA
    Annu Rev Biochem 75:567-605. 2006
  8. ncbi Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair
    Ivan M Munoz
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Mol Cell 35:116-27. 2009
  9. pmc Aberrant chromosome morphology in human cells defective for Holliday junction resolution
    Thomas Wechsler
    London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 471:642-6. 2011
  10. pmc Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia
    Gerry P Crossan
    Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK
    Nat Genet 43:147-52. 2011

Detail Information

Publications284 found, 100 shown here

  1. pmc Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases
    Samira Fekairi
    Genome Instability and Carcinogenesis UPR3081 CNRS, Conventionné par l Université d Aix Marseille 2, IGC, IMM 31 chemin Joseph Aiguier, 13402 Marseille, France
    Cell 138:78-89. 2009
    ..We propose that SLX4 acts as a docking platform for multiple structure-specific endonucleases...
  2. pmc Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair
    Jennifer M Svendsen
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 138:63-77. 2009
    ..Thus, SLX4 assembles a modular toolkit for repair of specific types of DNA lesions and is critical for cellular responses to replication fork failure...
  3. ncbi SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype
    Chantal Stoepker
    Department of Clinical Genetics, Vrije Universiteit VU Medical Center, Amsterdam, The Netherlands
    Nat Genet 43:138-41. 2011
    ..These individuals, who were previously diagnosed as having Fanconi anemia, add SLX4 as an essential component to the FA-BRCA genome maintenance pathway...
  4. ncbi Talking about a revolution: The impact of site-specific recombinases on genetic analyses in mice
    Catherine S Branda
    Harvard Medical School, Department of Genetics, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Dev Cell 6:7-28. 2004
    ..By enabling high-fidelity DNA modifications to be induced in vitro or in vivo, these systems have incited a wave of new biology, advancing our understanding of gene function, genetic relationships, development, and disease...
  5. pmc Chimeric TALE recombinases with programmable DNA sequence specificity
    Andrew C Mercer
    The Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Nucleic Acids Res 40:11163-72. 2012
    Site-specific recombinases are powerful tools for genome engineering...
  6. pmc Mutations of the SLX4 gene in Fanconi anemia
    Yonghwan Kim
    Laboratory of Genome Maintenance, The Rockefeller University, New York, New York, USA
    Nat Genet 43:142-6. 2011
    ....
  7. ncbi Mechanisms of site-specific recombination
    Nigel D F Grindley
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114, USA
    Annu Rev Biochem 75:567-605. 2006
    ..Virtually all identified site-specific recombinases fall into one of just two families, the tyrosine recombinases and the serine recombinases, named after the ..
  8. ncbi Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair
    Ivan M Munoz
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Mol Cell 35:116-27. 2009
    ..Depletion of SLX4 causes a decrease in DSB-induced homologous recombination. These data show that SLX4 is a regulator of structure-specific nucleases and that SLX4 and SLX1 are important regulators of genome stability in human cells...
  9. pmc Aberrant chromosome morphology in human cells defective for Holliday junction resolution
    Thomas Wechsler
    London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 471:642-6. 2011
    ....
  10. pmc Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia
    Gerry P Crossan
    Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK
    Nat Genet 43:147-52. 2011
    ..The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway...
  11. ncbi Serine recombinases as tools for genome engineering
    William R A Brown
    School of Biology, Queens Medical Centre, Nottingham NG7 2UH, UK
    Methods 53:372-9. 2011
    The serine recombinases differ mechanistically from the tyrosine recombinases and include proteins such as ϕC31 integrase which, unlike Cre and Flp, promote unidirectional reactions...
  12. pmc Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA structure-specific endonucleases in DNA repair and recombination
    Sabrina L Andersen
    Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    Mol Cell 35:128-35. 2009
    ..Genetic and biochemical evidence described here and in related papers suggest that MUS312 and BTBD12 direct Holliday junction resolution by at least two distinct endonucleases in different recombination and repair contexts...
  13. ncbi Diversity in the serine recombinases
    Margaret C M Smith
    Institute of Genetics, Queens Medical Centre, University of Nottingham, NG7 2UH, UK
    Mol Microbiol 44:299-307. 2002
    Most site-specific recombinases fall into one of two families, based on evolutionary and mechanistic relatedness. These are the tyrosine recombinases or lambda integrase family and the serine recombinases or resolvase/invertase family...
  14. ncbi Phage recombinases and their applications
    Kenan C Murphy
    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
    Adv Virus Res 83:367-414. 2012
    ..From the beginning, it was recognized that these recombinases are linked intimately to the mechanisms of phage DNA replication...
  15. ncbi Dre recombinase, like Cre, is a highly efficient site-specific recombinase in E. coli, mammalian cells and mice
    Konstantinos Anastassiadis
    Center for Regenerative Therapies Dresden, BioInnovationsZentrum Technische Universitaet Dresden, Am Tatzberg 47, 01307 Dresden, Germany
    Dis Model Mech 2:508-15. 2009
    Tyrosine site-specific recombinases (SSRs) including Cre and FLP are essential tools for DNA and genome engineering. Cre has long been recognized as the best SSR for genome engineering, particularly in mice...
  16. pmc Interactions between Mei4, Rec114, and other proteins required for meiotic DNA double-strand break formation in Saccharomyces cerevisiae
    Shohreh Maleki
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Chromosoma 116:471-86. 2007
    ..These studies also suggest that an essential function of Rec102 and Rec104 is to connect Mei4 and Rec114 to Spo11...
  17. pmc Zinc-finger recombinase activities in vitro
    Marko M Prorocic
    Institute of Infection, Immunity and Inflammation, University of Glasgow, GBRC, Glasgow G12 8QQ, Scotland, UK
    Nucleic Acids Res 39:9316-28. 2011
    Zinc-finger recombinases (ZFRs) are chimaeric proteins comprising a serine recombinase catalytic domain linked to a zinc-finger DNA binding domain...
  18. pmc G4 resolvase 1 binds both DNA and RNA tetramolecular quadruplex with high affinity and is the major source of tetramolecular quadruplex G4-DNA and G4-RNA resolving activity in HeLa cell lysates
    Steven D Creacy
    Department of Cancer Biology and the Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 283:34626-34. 2008
    ....
  19. pmc Identification and analysis of recombineering functions from Gram-negative and Gram-positive bacteria and their phages
    Simanti Datta
    Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA
    Proc Natl Acad Sci U S A 105:1626-31. 2008
    ..Beta and RecT are single-strand DNA annealing proteins, referred to here as recombinases. Each of the nine other genes when expressed in E. coli carries out oligonucleotide-mediated recombination...
  20. ncbi The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination
    Galina V Petukhova
    Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 5 Memorial Drive, Bethesda, Maryland 20892, USA
    Nat Struct Mol Biol 12:449-53. 2005
    ..Rad51 and Dmc1 recombinases are the major players in these processes...
  21. ncbi Recombinase-mediated cassette exchange (RMCE) - a rapidly-expanding toolbox for targeted genomic modifications
    Soeren Turan
    Hannover Medical School Institute for Experimental Hematology, OE 6960, Carl Neuberg Str 1, D 30625 Hannover, Germany
    Gene 515:1-27. 2013
    Starting in 1991, the advance of Tyr-recombinases Flp and Cre enabled superior strategies for the predictable insertion of transgenes into compatible target sites of mammalian cells...
  22. pmc Mammalian BTBD12 (SLX4) protects against genomic instability during mammalian spermatogenesis
    J Kim Holloway
    Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
    PLoS Genet 7:e1002094. 2011
    ..Taken together, these data indicate that BTBD12 functions throughout gametogenesis to maintain genome stability, possibly by co-ordinating repair processes and/or by linking DNA repair events to the cell cycle via ATM...
  23. ncbi Synapsis in phage Bxb1 integration: selection mechanism for the correct pair of recombination sites
    Pallavi Ghosh
    Pittsburgh Bacteriophage Institute and Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
    J Mol Biol 349:331-48. 2005
    Recombination by site-specific recombinases is a highly concerted process that requires synapsis of the correct pair of DNA substrates...
  24. ncbi Recombinational DNA double-strand breaks in mice precede synapsis
    S K Mahadevaiah
    Division of Developmental Genetics, National Institute for Medical Research, London, UK
    Nat Genet 27:271-6. 2001
    ..Loss of gamma-H2AX staining (which in irradiated somatic cells is temporally linked with DSB repair) is temporally and spatially correlated with synapsis, even when this synapsis is 'non-homologous'...
  25. pmc Saccharomyces cerevisiae Mer2, Mei4 and Rec114 form a complex required for meiotic double-strand break formation
    Jing Li
    Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, and Department of Genetics, Yale University, New Haven, Connecticut 06520 8103, USA
    Genetics 173:1969-81. 2006
    ..Mer2 does not show significant colocalization with Mre11 or Rec102 and Mer2 does not co-immunoprecipitate with Rec102. We propose that Mer2, Mei4, and Rec114 form a distinct complex required for DSB formation...
  26. pmc Expanding the scope of site-specific recombinases for genetic and metabolic engineering
    Thomas Gaj
    The Skaggs Institute for Chemical Biology and the Departments of Chemistry and Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, 92037
    Biotechnol Bioeng 111:1-15. 2014
    Site-specific recombinases are tremendously valuable tools for basic research and genetic engineering...
  27. pmc Characterization of a new SCCmec element in Staphylococcus cohnii
    Zhiyong Zong
    Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
    PLoS ONE 5:e14016. 2010
    ..Many SCCmec elements of coagulase-negative staphylococci (CoNS) could not be typed using multiplex PCR. Such a 'non-typable' SCCmec was encountered in a Staphylococcus cohnii isolate...
  28. pmc Detection of novel recombinases in bacteriophage genomes unveils Rad52, Rad51 and Gp2.5 remote homologs
    Anne Lopes
    CEA, iBiTecS, F 91191 Gif sur Yvette, France
    Nucleic Acids Res 38:3952-62. 2010
    ..structure-based modelling and gene-context analyses, we provide new views on the global landscape of recombinases in 465 bacteriophages...
  29. pmc VCre/VloxP and SCre/SloxP: new site-specific recombination systems for genome engineering
    Emiko Suzuki
    Department of Human Genome Research, Kazusa DNA Research Institute, Graduate School of Pharmaceutical Sciences, Chiba University, 2 6 7 Kazusa Kamatari, Kisarazu, Chiba 292 0818, Japan
    Nucleic Acids Res 39:e49. 2011
    ..Their recognition sites are different from Cre recognition sites because VCre and SCre recombinases share less protein similarity with Cre, even though the basic 13-8-13 structures of their recognition sites are ..
  30. ncbi Site-specific recombination by phiC31 integrase and other large serine recombinases
    Margaret C M Smith
    Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
    Biochem Soc Trans 38:388-94. 2010
    ..Integrases belong either to the lambda Int family of tyrosine recombinases or to a subgroup of the serine recombinases, the large serine recombinases...
  31. pmc The budding yeast mei5 and sae3 proteins act together with dmc1 during meiotic recombination
    Hideo Tsubouchi
    Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520 8103, USA
    Genetics 168:1219-30. 2004
    ..Taken together, these observations suggest that the Mei5 and Sae3 proteins are accessory factors specific to Dmc1. We speculate that Mei5 and Sae3 are necessary for efficient formation of Dmc1-containing nucleoprotein filaments in vivo...
  32. pmc Rad51 is an accessory factor for Dmc1-mediated joint molecule formation during meiosis
    Veronica Cloud
    Committee on Genetics, University of Chicago, Cummings Life Science Center, 920 East 58th Street, Chicago, IL 60637, USA
    Science 337:1222-5. 2012
    ..We further provide biochemical evidence that Rad51 acts with Mei5-Sae3 as a Dmc1 accessory factor. Thus, Rad51 is a multifunctional protein that catalyzes recombination directly in mitosis and indirectly, via Dmc1, during meiosis...
  33. ncbi Genome engineering using site-specific recombinases
    Andreas F Kolb
    Cell Physiology Group, Hannah Research Institute, Ayr, United Kingdom
    Cloning Stem Cells 4:65-80. 2002
    ..Site-specific recombinases have become significant tools in all of these areas...
  34. pmc G4 resolvase 1 tightly binds and unwinds unimolecular G4-DNA
    Banabihari Giri
    Department of Cancer Biology and the Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston Salem, USA
    Nucleic Acids Res 39:7161-78. 2011
    ..This report provides evidence that G4R1/RHAU tightly binds and unwinds unimolecular G4-DNA structures...
  35. ncbi Efficient point mutagenesis in mycobacteria using single-stranded DNA recombineering: characterization of antimycobacterial drug targets
    Julia C van Kessel
    Pittsburgh Bacteriophage Institute and Department of Biological Sciences, 376 Crawford Hall, 4249 Fifth Ave, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Mol Microbiol 67:1094-107. 2008
    ..This ssDNA recombineering provides a simple assay for comparing the activities of related phage recombinases, and we find that both Escherichia coli RecET and phage lambda Red recombination proteins function ..
  36. ncbi Structure, function, and evolution of linear replicons in Borrelia
    George Chaconas
    Department of Biochemistry and Molecular Biology, The University of Calgary, Calgary, AB T2N 4N1, Canada
    Annu Rev Microbiol 64:185-202. 2010
    ..Telomere resolvases are related to the tyrosine recombinases and ResT can generate the crucial reaction intermediate of this class of enzyme, the Holliday junction...
  37. pmc Regulation of type 1 fimbriae by unlinked FimB- and FimE-like recombinases in uropathogenic Escherichia coli strain CFT073
    Andrew Bryan
    Department of Medical Microbiology and Immunology, University of Wisconsin Madison, Madison, WI 53706, USA
    Infect Immun 74:1072-83. 2006
    ..Alignment of the predicted amino acid sequences showed that the five recombinases range in sequence similarity from 63 to 70%...
  38. pmc Multiple staphylococcal cassette chromosomes and allelic variants of cassette chromosome recombinases in Staphylococcus aureus and coagulase-negative staphylococci from Norway
    Anne Merethe Hanssen
    Department of Microbiology and Virology, Faculty of Medicine, Institute of Medical Biology, University of Tromsø, Tromsø, Norway
    Antimicrob Agents Chemother 51:1671-7. 2007
    ..The enormous diversity observed in the SCCmec elements implies a large SCCmec reservoir in CoNS...
  39. ncbi The Swi5-Sfr1 complex stimulates Rhp51/Rad51- and Dmc1-mediated DNA strand exchange in vitro
    Nami Haruta
    Division of Molecular and Cellular Biology, International Graduate School of Arts and Sciences, Yokohama City University, 1 7 29 Suehiro cho, Tsurumi, Yokohama, Kanagawa 230 0045, Japan
    Nat Struct Mol Biol 13:823-30. 2006
    Nucleoprotein filaments made up of Rad51 or Dmc1 recombinases, the core structures of recombination, engage in ATP-dependent DNA-strand exchange...
  40. ncbi Characterization of XerC- and XerD-dependent CTX phage integration in Vibrio cholerae
    Sarah M McLeod
    Department of Molecular Biology and Microbiology, Tufts University School of Medicine and Howard Hughes Medical Institute, Boston, MA 02111, USA
    Mol Microbiol 54:935-47. 2004
    ..The CTXphi genome lacks an integrase; instead, its integration depends on the chromosome-encoded tyrosine recombinases XerC and XerD. During integration, recombination occurs between regions of homology in CTXphi and the V...
  41. pmc Molecular basis for enhancement of the meiotic DMC1 recombinase by RAD51 associated protein 1 (RAD51AP1)
    Eloïse Dray
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 108:3560-5. 2011
    ..These results suggest that RAD51AP1 also serves an important role in meiotic homologous recombination...
  42. pmc The ripX locus of Bacillus subtilis encodes a site-specific recombinase involved in proper chromosome partitioning
    S A Sciochetti
    Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
    J Bacteriol 181:6053-62. 1999
    ..Bacillus subtilis ripX gene encodes a protein that has 37 and 44% identity with the XerC and XerD site-specific recombinases of Escherichia coli...
  43. pmc Efficient conditional and promoter-specific in vivo expression of cDNAs of choice by taking advantage of recombinase-mediated cassette exchange using FlEx gene traps
    Laura Schebelle
    Helmholtz Zentrum Munchen, Technische Universitat Munchen, Institut für Entwicklungsgenetik, Ingolstadter Landstrasse 1, 85764 München, Neuherberg, Germany
    Nucleic Acids Res 38:e106. 2010
    ..The use of the RMCE system presented in this work requires one single-cloning step followed by one overnight gateway clonase reaction and subsequent cassette exchange in ES cells with efficiencies of 40% in average...
  44. pmc Targeted plasmid integration into the human genome by an engineered zinc-finger recombinase
    Charles A Gersbach
    The Skaggs Institute for Chemical Biology, Department of Molecular Biology, CA, USA
    Nucleic Acids Res 39:7868-78. 2011
    ..This work demonstrates the potential for broad applicability of the ZFR technology in genome engineering, synthetic biology and gene therapy...
  45. ncbi PhiC31 integrase facilitates genetic approaches combining multiple recombinases
    Claudio Monetti
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
    Methods 53:380-5. 2011
    Homologous and site-specific DNA recombination has revolutionized genetic engineering. The reliability of recombinases such as Cre and FLP has allowed scientists to design complex strategies to study gene function in mammals...
  46. pmc A comprehensive approach to zinc-finger recombinase customization enables genomic targeting in human cells
    Thomas Gaj
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Nucleic Acids Res 41:3937-46. 2013
    Zinc-finger recombinases (ZFRs) represent a potentially powerful class of tools for targeted genetic engineering...
  47. ncbi A new group of tyrosine recombinase-encoding retrotransposons
    Timothy J D Goodwin
    Department of Biochemistry, University of Otago, Dunedin, New Zealand
    Mol Biol Evol 21:746-59. 2004
    ..In addition they contain elements with some surprising features, such as spliceosomal introns and long overlapping open reading frames...
  48. pmc Roles of two large serine recombinases in mobilizing the methicillin-resistance cassette SCCmec
    Agnieszka Misiura
    Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA
    Mol Microbiol 88:1218-29. 2013
    ..Most variants of SCCmec encode two recombinases, CcrA and CcrB, that belong to the large serine family...
  49. pmc Stimulation of fission yeast and mouse Hop2-Mnd1 of the Dmc1 and Rad51 recombinases
    Mickael Ploquin
    Genome Stability Laboratory, Laval University Cancer Research Center, Hotel Dieu de Quebec, 9 McMahon, Quebec City, QC, Canada G1R 2J6
    Nucleic Acids Res 35:2719-33. 2007
    ..that while spHop2-Mnd1 affects spDmc1 specifically, mHop2 or mHop2-Mnd1 stimulates both the hRad51 and hDmc1 recombinases in strand exchange assays. Thus, our results suggest a crucial role for S...
  50. ncbi Catalytic residues of the telomere resolvase ResT: a pattern similar to, but distinct from, tyrosine recombinases and type IB topoisomerases
    Jan Deneke
    Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 1N4, Canada
    J Biol Chem 279:53699-706. 2004
    ..have shown that ResT catalyzes hairpin formation through a two-step transesterification similar to tyrosine recombinases and type IB topoisomerases. In the present study we have probed the reaction mechanism of ResT...
  51. ncbi In vitro evolution and analysis of HIV-1 LTR-specific recombinases
    Frank Buchholz
    Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
    Methods 53:102-9. 2011
    ..We furthermore provide protocols that are utilized for the investigation of Tre's antiretroviral activity in infected tissue cultures as well as in infected humanized Rag2(-/-)γc(-/-) mice...
  52. ncbi Mutation analysis of the SLX4/FANCP gene in hereditary breast cancer
    Rosa Landwehr
    Clinics of Obstetrics and Gynaecology, Hannover Medical School, Carl Neuberg Str 1, 30625 Hannover, Germany
    Breast Cancer Res Treat 130:1021-8. 2011
    ..G700R substitution could make a minor contribution...
  53. pmc Synthesis of programmable integrases
    Russell M Gordley
    Departments of Molecular Biology and Chemistry and The Skaggs Institute for Chemical Biology, BCC 550, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 106:5053-8. 2009
    ..We generated chimeric zinc finger recombinases with cooperative DNA-binding and catalytic specificities that integrate transgenes with >98% accuracy into ..
  54. ncbi Identification and molecular characterisation of DNA damaging agent induced expression of Plasmodium falciparum recombination protein PfRad51
    Mrinal Kanti Bhattacharyya
    Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD 21205, USA
    Int J Parasitol 33:1385-92. 2003
    ..PfRad51 is the first apicomplexan gene identified that codes for a recombination protein, and it offers an excellent model for studying DNA damage inducible gene expression in such parasites...
  55. ncbi The DEXH protein product of the DHX36 gene is the major source of tetramolecular quadruplex G4-DNA resolving activity in HeLa cell lysates
    James P Vaughn
    Department of Cancer Biology and the Comprehensive Cancer Center of Wake Forest Medical Center, Winston Salem, North Carolina 27157, USA
    J Biol Chem 280:38117-20. 2005
    ..77% of the enzyme from lysates and reduced G4-DNA resolving activity to 46.0 +/- 0.4% of control, demonstrating that DHX36 protein is responsible for the majority of tetramolecular G4-DNA resolvase activity...
  56. ncbi Method for Bxb1-mediated site-specific integration in planta
    Yuan Yeu Yau
    Plant Gene Expression Center, USDA ARS and Plant and Microbial Biology, University of California Berkeley, Albany, CA, USA
    Methods Mol Biol 701:147-66. 2011
    ..This method would permit the comparison of different molecular constructs at the same genomic locations...
  57. ncbi Regulation of DNA strand exchange in homologous recombination
    J Thomas Holthausen
    Department of Cell Biology and Genetics, Cancer Genomics Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
    DNA Repair (Amst) 9:1264-72. 2010
    ..The function of recombinases is controlled by accessory proteins that allow coordination of strand exchange with other steps of homologous ..
  58. pmc SeLOX--a locus of recombination site search tool for the detection and directed evolution of site-specific recombination systems
    Vineeth Surendranath
    Max Planck Institute for the Molecular Cell Biology and Genetics, Dresden, Germany
    Nucleic Acids Res 38:W293-8. 2010
    Site-specific recombinases have become a resourceful tool for genome engineering, allowing sophisticated in vivo DNA modifications and rearrangements, including the precise removal of integrated retroviruses from host genomes...
  59. pmc Zinc finger recombinases with adaptable DNA sequence specificity
    Chris Proudfoot
    College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom
    PLoS ONE 6:e19537. 2011
    Site-specific recombinases have become essential tools in genetics and molecular biology for the precise excision or integration of DNA sequences...
  60. pmc Directed evolution of recombinase specificity by split gene reassembly
    Charles A Gersbach
    The Skaggs Institute for Chemical Biology, Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Nucleic Acids Res 38:4198-206. 2010
    ..To address this need, we developed a robust strategy for evolving site-specific recombinases with novel substrate specificities...
  61. ncbi Resolution of holliday junctions by RuvABC prevents dimer formation in rep mutants and UV-irradiated cells
    B Michel
    Génétique Microbienne, INRA, 78352 Jouy en Josas Cedex, France
    Mol Microbiol 37:180-91. 2000
    ..We conclude that the inviability arising from a high frequency of dimer formation in rep or UV-irradiated cells is only observed in the absence of known enzymes that resolve Holliday junctions...
  62. pmc FtsK-dependent dimer resolution on multiple chromosomes in the pathogen Vibrio cholerae
    Marie Eve Val
    CNRS, Centre de Genetique Moleculaire, UPR 2167, Gif sur Yvette, France
    PLoS Genet 4:e1000201. 2008
    ..coli, chromosome dimers are resolved by the addition of a crossover at a specific site, dif, by two tyrosine recombinases, XerC and XerD. The process is coordinated with cell division through the activity of a DNA translocase, FtsK...
  63. pmc Measuring chromosome dynamics on different time scales using resolvases with varying half-lives
    Richard A Stein
    Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Mol Microbiol 56:1049-61. 2005
    ..Rather than the 150 domains detected with the Tn3 resolvase, wild-type cells measured over a 10 min time span have more than 400 domains per genome equivalent, and some gyrase mutants exceed 1000...
  64. ncbi Evolution of programmable zinc finger-recombinases with activity in human cells
    Russell M Gordley
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Mol Biol 367:802-13. 2007
    Site-specific recombinases are important tools for genomic engineering in many living systems. Applications of recombinases are, however, constrained by the DNA targeting endemic of the recombinase used...
  65. ncbi Distribution of the ACME-arcA gene among meticillin-resistant Staphylococcus haemolyticus and identification of a novel ccr allotype in ACME-arcA-positive isolates
    Borui Pi
    State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China
    J Med Microbiol 58:731-6. 2009
    ..The results from this study revealed that MRSH is likely to be one of the potential reservoirs of ACME for Staphylococcus aureus...
  66. ncbi The structure of the excisionase (Xis) protein from conjugative transposon Tn916 provides insights into the regulation of heterobivalent tyrosine recombinases
    Mohamad Abbani
    Department of Chemistry and Biochemistry, UCLA DOE Institute of Genomics and Proteomics, and the Molecular Biology Institute, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095 1570, USA
    J Mol Biol 347:11-25. 2005
    Heterobivalent tyrosine recombinases play a prominent role in numerous bacteriophage and transposon recombination systems...
  67. pmc Novel type V staphylococcal cassette chromosome mec driven by a novel cassette chromosome recombinase, ccrC
    Teruyo Ito
    Department of Bacteriology, Faculty of Medicine, Juntendo University, 2 1 1 Hongo, Bunkyo ku, Tokyo, Japan
    Antimicrob Agents Chemother 48:2637-51. 2004
    ..of the mec gene complex, which encodes methicillin resistance, and the ccr gene complex, which encodes the recombinases responsible for its mobility...
  68. pmc Structure-guided reprogramming of serine recombinase DNA sequence specificity
    Thomas Gaj
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 108:498-503. 2011
    ..These results demonstrate that unique resolvase and invertase derivatives can be developed to site-specifically modify the human genome in the context of zinc-finger recombinase fusion proteins...
  69. ncbi Transgene manipulation in zebrafish by using recombinases
    Jie Dong
    Department of Life Sciences, Indiana State University, Terre Haute, Indiana 47809, USA
    Methods Cell Biol 77:363-79. 2004
    ..g., phiC31 integrase) can improve the utility of this system. After the fish system is fully established, it would be interesting to explore its application to genome engineering in other organisms...
  70. ncbi Strand selection by the tyrosine recombinases
    Linda Lee
    Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA
    Prog Nucleic Acid Res Mol Biol 80:1-42. 2005
  71. ncbi Norfloxacin-induced DNA cleavage occurs at the dif resolvase locus in Escherichia coli and is the result of interaction with topoisomerase IV
    A Hojgaard
    Department of Pathology, University of Utah, Salt Lake City 84112, USA
    Mol Microbiol 33:1027-36. 1999
    ..This interaction required XerC and XerD, but did not require the C-terminal region of FtsK or cell division...
  72. ncbi Efficient DNA cassette exchange in mouse embryonic stem cells by staggered positive-negative selection
    Qiaoming Long
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    Genesis 39:256-62. 2004
    ..This selection strategy, by facilitating more efficient production of ES cell clones with various replacement DNA cassettes, should accelerate targeted repetitive introduction of gene modifications into the mouse...
  73. pmc Xer1-mediated site-specific DNA inversions and excisions in Mycoplasma agalactiae
    Stefan Czurda
    Institute of Bacteriology, Mycology and Hygiene IBMH, Department of Pathobiology, University of Veterinary Medicine Vienna, Veterinaerplatz 1, Vienna, Austria
    J Bacteriol 192:4462-73. 2010
    ..Unless there are specific regulatory mechanisms preventing such excisions, this might be the cost that the pathogen has to render at the population level for maintaining this high-frequency phase variation machinery...
  74. pmc Hallmarks of homology recognition by RecA-like recombinases are exhibited by the unrelated Escherichia coli RecT protein
    Philippe Noirot
    Laboratoire de Genetique Microbienne, INRA, 78352 Jouy en Josas Cedex, France
    EMBO J 22:324-34. 2003
    ..Taken together, our results show that RecT shares fundamental homology-recognition properties with the RecA homologs, and provide new insights on an underlying universal mechanism of homologous recognition...
  75. pmc Arginine as a general acid catalyst in serine recombinase-mediated DNA cleavage
    Ross A Keenholtz
    From the Department of Biochemistry and Molecular Biology and
    J Biol Chem 288:29206-14. 2013
    Members of the serine family of site-specific DNA recombinases use an unusual constellation of amino acids to catalyze the formation and resolution of a covalent protein-DNA intermediate...
  76. pmc Use of the lambda Red recombinase system to rapidly generate mutants in Pseudomonas aeruginosa
    Biliana Lesic
    Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA
    BMC Mol Biol 9:20. 2008
    ....
  77. pmc Characterization of a complex context containing mecA but lacking genes encoding cassette chromosome recombinases in Staphylococcus haemolyticus
    Zhiyong Zong
    Center of Infectious Diseases, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, China
    BMC Microbiol 13:64. 2013
    ..However, the mecA gene might not be carried by a SCCmec in a Staphylococcus haemolyticus clinical isolate, WCH1, as no cassette chromosome recombinase genes were detected. Therefore, the genetic context of mecA in WCH1 was investigated...
  78. ncbi HUH site-specific recombinases for targeted modification of the human genome
    Coral González-Prieto
    Departamento de Biología Molecular Universidad de Cantabria and IBBTEC UC, CSIC, SODERCAN, Santander, Spain
    Trends Biotechnol 31:305-12. 2013
    Site-specific recombinases (SSRs) have been crucial in the development of mammalian transgenesis...
  79. pmc A phylogenomic study of DNA repair genes, proteins, and processes
    J A Eisen
    Department of Biological Sciences, Stanford University, Stanford, CA 94305 5020, USA
    Mutat Res 435:171-213. 1999
    ..We use this phylogenomic analysis to study the evolution of repair proteins and processes and to predict the repair phenotypes of those species for which we now know the complete genome sequence...
  80. pmc Lactococcal phage genes involved in sensitivity to AbiK and their relation to single-strand annealing proteins
    Julie D Bouchard
    Departement de Biochimie et de Microbiologie, Faculté de Sciences et de Génie, Groupe de Recherche en Ecologie Buccale GREB, Faculte de Medecine Dentaire, Universite Laval, Quebec, Canada G1K 7P4
    J Bacteriol 186:3649-52. 2004
    ..Four nonsimilar proteins involved in the sensitivity to AbiK (Sak) were identified. Two of these Sak proteins are related to Erf and RAD52, single-strand annealing proteins involved in homologous recombination...
  81. ncbi The mu transpososome through a topological lens
    Rasika M Harshey
    Section of Molecular Genetics and Microbiology and Institute of Cellular and Molecular Biology, University of Texas at Austin, TX, USA
    Crit Rev Biochem Mol Biol 41:387-405. 2006
    ..This methodology has also revealed the order and dynamics of association of the three interacting DNA sites, as well as the role of the enhancer in assembly of the Mu transpososome...
  82. ncbi C-terminal interactions between the XerC and XerD site-specific recombinases
    A J Spiers
    Division of Molecular Genetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Mol Microbiol 32:1031-42. 1999
    ..By extrapolating the Cre DNA recombinase structure to the related site-specific recombinases XerC and XerD, it is predicted that the extreme C-termini of XerC and XerD interact with alpha-helix M in XerD ..
  83. ncbi Strategies for the use of site-specific recombinases in genome engineering
    Julie R Jones
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
    Methods Mol Med 103:245-57. 2005
    ..Strategies that make use of site-specific recombinases such as Cre and/or Flp have been developed in recent years to overcome these limitations...
  84. pmc Action of site-specific recombinases XerC and XerD on tethered Holliday junctions
    L K Arciszewska
    Department of Biochemistry, University of Oxford, UK
    EMBO J 16:3731-43. 1997
    In Xer site-specific recombination, two related recombinases, XerC and XerD, mediate the formation of recombinant products using Holliday junction-containing DNA molecules as reaction intermediates...
  85. ncbi Two site-specific recombinases are implicated in phenotypic variation and competitive rhizosphere colonization in Pseudomonas fluorescens
    Francisco Martínez-Granero
    Departamento de Biologia, Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid, Spain
    Microbiology 151:975-83. 2005
    ..variants under both culture and rhizosphere colonization conditions, implying that both site-specific recombinases are involved in phenotypic variation...
  86. pmc Site-specific recombinase genes in three Shigella subgroups and nucleotide sequences of a pinB gene and an invertible B segment from Shigella boydii
    A Tominaga
    Department of Biology, Faculty of Science, Okayama University, Japan
    J Bacteriol 173:4079-87. 1991
    ..The defective pinF gene is suggested to hae the same origin as P-pin on e14 by the restriction map of the fragment cloned from a Pin+ transductant that was obtained in transduction from S. flexneri to E. coli delta pin...
  87. ncbi Resolving integral questions in site-specific recombination
    Phoebe A Rice
    Nat Struct Mol Biol 12:641-3. 2005
  88. ncbi New insights into host factor requirements for prokaryotic beta-recombinase-mediated reactions in mammalian cells
    V Diaz
    Departamento de Inmunologia y Oncologia and Biotecnologia Microbiana, Centro Nacional de Biotecnologia, CSIC, , Cantoblanco, E-28049 Madrid, Spain
    J Biol Chem 276:16257-64. 2001
    ..These data demonstrate the existence of cellular factors different from HMG-1 that can act as helpers for beta-recombinase activity in the eukaryotic environment...
  89. pmc Chimeric recombinases with designed DNA sequence recognition
    Aram Akopian
    Institute of Biomedical and Life Sciences, University of Glasgow, 56 Dumbarton Road, Glasgow G11 6NU, Scotland
    Proc Natl Acad Sci U S A 100:8688-91. 2003
    ..We describe chimeric recombinases with a catalytic domain from an activated multiple mutant of the bacterial enzyme Tn3 resolvase, fused to a DNA ..
  90. ncbi Elimination of selection markers from transgenic plants
    B Hohn
    Friedrich Miescher Institute, Maulbeerstrasse 66, 4058 Basel, Switzerland
    Curr Opin Biotechnol 12:139-43. 2001
    ..Regimes to achieve their efficient elimination, mostly through site-specific recombination or transposition, are being developed...
  91. ncbi Excision of selectable marker genes from transgenic plants
    Peter D Hare
    Laboratory of Plant Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Nat Biotechnol 20:575-80. 2002
    ..The implementation of these strategies in crops and their further improvement will help to expedite widespread public acceptance of agricultural biotechnology..
  92. ncbi ParA resolvase catalyzes site-specific excision of DNA from the Arabidopsis genome
    James G Thomson
    Plant Gene Expression Center, 800 Buchanan Street, Albany, CA 94710, USA
    Transgenic Res 18:237-48. 2009
    ....
  93. ncbi Cryptons: a group of tyrosine-recombinase-encoding DNA transposons from pathogenic fungi
    Timothy J D Goodwin
    Department of Biochemistry, University of Otago, Cumberland Street, Dunedin, New Zealand
    Microbiology 149:3099-109. 2003
    ..Sequence comparisons suggest that cryptons may be related to the DIRS1 and Ngaro1 groups of tyrosine-recombinase-encoding retrotransposons...
  94. pmc FtsK functions in the processing of a Holliday junction intermediate during bacterial chromosome segregation
    F X Barre
    Division of Molecular Genetics, Department of Biochemistry, University of Oxford, OX1 3QU, UK
    Genes Dev 14:2976-88. 2000
    ..region of the chromosome, converts dimers to monomers through the sequential action of the XerC and XerD recombinases. Chromosome dimer resolution requires that dif is positioned correctly in the chromosome, and the activity of ..
  95. pmc Challenging a paradigm: the role of DNA homology in tyrosine recombinase reactions
    Lara Rajeev
    Department of Civil and Environmental Engineering, University of Washington, Seattle, Washington 98125, USA
    Microbiol Mol Biol Rev 73:300-9. 2009
    ..catalyzing site-specific recombination, as exemplified by the phage lambda integrase and the Cre and Flp recombinases, is the ability to recombine substrates sharing very limited DNA sequence identity...
  96. pmc DNA replication meets genetic exchange: chromosomal damage and its repair by homologous recombination
    A Kuzminov
    Department of Microbiology, University of Illinois, Urbana Champaign, B103, Chemical and Life Sciences Laboratory, 601 South Goodwin Avenue, Urbana, IL 61801 3709, USA
    Proc Natl Acad Sci U S A 98:8461-8. 2001
    ..In vitro properties of the eukaryotic recombinases suggest a bigger role for single-strand annealing in the eukaryotic recombinational repair.
  97. ncbi FtsK Is a DNA motor protein that activates chromosome dimer resolution by switching the catalytic state of the XerC and XerD recombinases
    Laurent Aussel
    Division of Molecular Genetics, Department of Biochemistry, University of Oxford, OX1 3QU, Oxford, United Kingdom
    Cell 108:195-205. 2002
    ..a complete Xer recombination reaction between dif sites by switching the state of activity of the XerCD recombinases so that XerD makes the first pair of strand exchanges to form Holliday junctions that are then resolved by XerC...
  98. pmc Crystal structure of the site-specific recombinase, XerD
    H S Subramanya
    Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK
    EMBO J 16:5178-87. 1997
    ....
  99. pmc Flexibility in DNA recombination: structure of the lambda integrase catalytic core
    H J Kwon
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA 02115, USA
    Science 276:126-31. 1997
    Lambda integrase is archetypic of site-specific recombinases that catalyze intermolecular DNA rearrangements without energetic input...
  100. ncbi Tyrosine site-specific recombinases mediate DNA inversions affecting the expression of outer surface proteins of Bacteroides fragilis
    Katja G Weinacht
    Channing Laboratory, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
    Mol Microbiol 53:1319-30. 2004
    ....
  101. ncbi Interactions of the Caulobacter crescentus XerC and XerD recombinases with the E. coli dif site
    Loubna Jouan
    Departement de Microbiologie et Immunologie, Universite de Montreal, C P 6128 Succ Centre Ville, Montreal, QC, Canada H3C3J7
    FEMS Microbiol Lett 222:257-62. 2003
    ..These dimers are then resolved by the action of the XerC and XerD recombinases, which act on the chromosomal dif site in the presence of the FtsK cell division protein...

Research Grants73

  1. Transcription factors regulating sensory gene expression and pain pathways
    Eric E Turner; Fiscal Year: 2011
    ..Together these studies will significantly advance our understanding of the molecular regulation of pain receptor pathways, which may form the basis for future pain treatments. ..
  2. Autonomic and Antihypertensive Actions of Neuronal CGRP/RAMP1 Receptors
    Mark W Chapleau; Fiscal Year: 2013
    ..Inhibition of Ang II-mediated effects by activation of CGRP/RAMP1 receptors has widespread implications in hypertension and heart failure. ..
  3. Monitoring cellular redox signaling and oxidant stress in vivo
    Paul T Schumacker; Fiscal Year: 2010
    ..The end result should significantly extend our ability to assess ROS in intact tissues, in animal models of disease. ..
  4. Cre, Dre Dual Lineage Model for Calcium Imaging and Optogenetic Manipulations
    Petr Tvrdik; Fiscal Year: 2013
    ..We will be able to determine if Hoxb8 mutant microglia respond to neural stimuli correctly. Taken together, the proposed work will advance the set of tools available to address the underlying causes of glial and other disorders. ..
  5. P38 MAP KINASE SIGNALING IN SKIN
    Tatiana Efimova; Fiscal Year: 2013
    ..We are optimistic that the completion of the proposed studies will result in a better mechanistic understanding of the p384 role in epithelial carcinogenesis and its potential as an anti-cancer therapeutic target. ..
  6. Conditional Knockout of Calcium Receptors in Bone Cells
    Dolores M Shoback; Fiscal Year: 2013
    ....
  7. VEGF Regulation of Hepatic Erythropoietin Synthesis
    Calvin Kuo; Fiscal Year: 2009
    ....
  8. Inducible Macrophage Specific Gene Expression in Diseases
    JEANINE M D apos ARMIENTO; Fiscal Year: 2010
    ..We will also examine the consequences of the absence of macrophage tissue inhibitor of metalloproteinases-3 in lung injury. ..
  9. Mitochondrial Oxidative Stress in the Retinal Pigment Epithelium as a Model for A
    Alfred S Lewin; Fiscal Year: 2013
    ..This project seeks to establish a mouse model of the pathology related to AMD and to use this model to test potential therapies for the atrophic form of the disease. ..
  10. Developmental Programs of Neural Circuits in the Mouse Medial Hypothalamus
    Holly A Ingraham; Fiscal Year: 2013
    ..Accordingly, results from the proposed studies may provide a new arsenal to combat the growing and costly effects of obesity and Type 2 diabetes. ..
  11. Regulation of the VDJ recombinase during genotoxic stress
    Karla K Rodgers; Fiscal Year: 2013
    ..The ability to enhance such a regulatory process may lead to decreased risks of developing lymphoid malignancies following exposure to radiation and other DNA damaging drugs. ..
  12. Regulation of Lung Fibrosis by Alternatively Activated Macrophages and Arginase-1
    ROBERT MATTHEW TIGHE; Fiscal Year: 2013
    ..Collectively, this approach will allow us to dissect the role of arginase-1 production by macrophages and fibroblasts in the pathobiology of progressive pulmonary fibrosis. ..
  13. Inducible recombination and gene expression in specific neurotransmitter systems
    Steven A Thomas; Fiscal Year: 2012
    ..It is expected that the proposed mouse models will permit significant insights into the etiology, identification and treatment of these disorders. ..
  14. Is symmetrical dimethylation of Arginine 2 of Histone H3 used as an epigenetic si
    Marjorie A Oettinger; Fiscal Year: 2010
    ..The experiments proposed here should define the roles of this modification and lead to insights into its possible role in both normal development and human disease. ..
  15. Modeling schizophrenia gamma deficits using cell-specific RNAi knockdown of GAD67
    RITCHIE EDWARD BROWN; Fiscal Year: 2012
    ....
  16. Generation of Site-Specific Recombinase-Expressing Transgenic Rats using an Enhan
    Eric M Ostertag; Fiscal Year: 2011
    ..The results from this study will generate valuable genetic tools for refined and subtle investigations of gene function in specific tissues. ..
  17. Mechanisms for the Effects of Hypothalamic PTP1B on Energy Balance
    KARYN JOANNE CATALANO; Fiscal Year: 2010
    ..By attempting to determine the specific neurons critical in these pathways, we hope to bring research closer to developing effective treatments for obesity with minimal side effects. ..
  18. Genetic correction of human beta-thalassemic induced pluripotent stem cells
    EIRINI PAPAPETROU; Fiscal Year: 2012
    ..abstract_text> ..
  19. Targeted investigation of tissue specific oxidative stress in the etiology of ALS
    Holly Van Remmen; Fiscal Year: 2013
    ....
  20. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    Nancy M Hollingsworth; Fiscal Year: 2013
    ..In budding yeast and mammals, there are two recombinases required for interhomolog (IH) recombination, the meiosis-specific Dmc1 protein and Rad51, which is also used ..
  21. CRP, eNOS and Endothelial Dysfunction
    Philip W Shaul; Fiscal Year: 2010
    ..The proposed research program will determine how CRP and its cell surface receptors cause hypertension and insulin resistance. ..
  22. Role of Gsalpha in Regulating Osteoblast Differentiation
    JOY Y WU; Fiscal Year: 2012
    ..Finally, Aim 3 will focus on determining the ability of osteoprogenitors to differentiate towards other mesenchymal lineages such as adipocytes, using lineage tracing in vivo and cell differentiation assays in vitro. ..
  23. Neurochemistry/physiology of proopiomelanocortin neurons
    MALCOLM JAMES LOW; Fiscal Year: 2013
    ....
  24. The Role of Complement in Airway Microvascular Disease
    MARK ROBERT NICOLLS; Fiscal Year: 2013
    ..Preventing airway ischemia through knowledge gained about complement activity and regulation in rejection may promote useful and potentially life-saving therapies for lung transplant recipients. ..
  25. A cell-specific inducible model of hearing loss
    Albert S Edge; Fiscal Year: 2011
    ..Because of the clear correlation between loss of cochlear cells and sensorineural hearing loss, improvements in our ability to regenerate these cells will lead directly to new treatments for loss of hearing. ..
  26. Long-Range Genetic and Epigenetic Control of Igh Gene Assembly
    Eugene M Oltz; Fiscal Year: 2010
    ..We propose studies to address how precursor B cells control long-range changes in the spatial organization of the immunoglobulin heavy chain locus to ensure its proper assembly and pursuant generation of an adaptive immune system. ..
  27. Function of the Zinc Finger Protein ZPR1 in neurodegeneration
    LAXMAN DASS GANGWANI; Fiscal Year: 2013
    ..Identification of ZPR1 as protective modifier of SMA will allow development of novel strategies for the treatment of SMA. ..
  28. Encapsidation of the poxvirus genome
    Paula Traktman; Fiscal Year: 2012
    ..Our investigations of genome encapsidation will provide fundamental insights into this poorly understood facet of the viral life cycle and define new targets for the development of rational antiviral therapies. ..
  29. The Significance of Leptin Signals to Neonatal Somatotropes and Gonadotropes
    Gwen V Childs; Fiscal Year: 2013
    ..This proposal thus addresses important questions about how leptin can affect reproductive competence at the level of the pituitary. ..
  30. Mouse Models to Characterize the Role of Lrp6 in Metabolic Syndrome
    Bart O Williams; Fiscal Year: 2010
    ..Given that cardiovascular disease is the leading killer in the United States, this work will be very significant in gaining a better understanding of the underlying causes of this disease. ..
  31. Genetic correction of human beta-thalassemic induced pluripotent stem cells
    EIRINI PAPAPETROU; Fiscal Year: 2013
    ..abstract_text> ..
  32. Analysis of the Human c-myc Gene Replication Origin
    Michael Leffak; Fiscal Year: 2012
    ..Thus, our studies are likely to provide fundamental new insight into the mechanisms of DNA replication, the origins of genetic diseases, and new models for disease treatment. ..
  33. Mechanisms and regulation of serine resolvases
    Phoebe A Rice; Fiscal Year: 2012
    ..goal of this work is to understand, in molecular detail, the regulation and catalytic mechanism of serine recombinases. These site-specific DNA recombinases are widespread in prokaryotes and perform a wide variety of genetic ..
  34. Functional role of RAG2 H3K4me3 interaction in V(D)J recombination
    Marjorie A Oettinger; Fiscal Year: 2013
    ..Our goal is to understand the normal steps in development and how errors in the process lead to immune deficiency syndromes and lymphoid tumors, with the hope of preventing or treating such diseases. ..
  35. Role of ROS-Induced DNA Damage in Mitochondria-Regulated Apoptosis
    Anne Tann; Fiscal Year: 2012
    ..Since alterations of this mechanism seem to help cancer cells to evade apoptosis, our findings could help design new therapeutic approaches for preventing and treating cancer. ..
  36. Cthrc1 function as a novel TGF-beta antagonist in the vasculature
    Volkhard Lindner; Fiscal Year: 2013
    ..With its ability to inhibit collagen production, Cthrc1 could be very suitable for the development of future antifibrotic therapies. ..
  37. c-Myc transcription in intestinal growth, differentiation, and carcinogenesis
    Gregory S Yochum; Fiscal Year: 2012
    ..Our studies address the fundamental mechanisms underlying b-catenin regulation of normal gastrointestinal development and homeostasis as well as the pathogenesis of intestinal malignancy. ..
  38. CRCNS: Theory and experiment of neural circuit mapping by DNA sequencing
    Anthony M Zador; Fiscal Year: 2013
    ..Using enzymes called DNA recombinases, we connect barcodes from the host cell to the invader barcodes that travel across synapses into pairs...
  39. The Kiss1 system in the neuroendocrine control of reproduction
    VICTOR MANUEL NAVARRO; Fiscal Year: 2013
    ..This additional training will aid in my development of a competitive research program and contribute to my establishment as an independent investigator. ..
  40. The Biosynthesis of Anandamide
    Dale G Deutsch; Fiscal Year: 2010
    ....
  41. Molecular-Genetic Dissection of Basal Forebrain Circuitry Regulating Arousal
    PATRICK MICHAEL FULLER; Fiscal Year: 2013
    ....
  42. The Role of Kappa Opioid Receptor-induced Activation of Astrocytes in the Reinsta
    Charles Chavkin; Fiscal Year: 2009
    ..This study would identify the connection between astrocyte activation and reinstatement of extinguished cocaine place preference by assessing the effects of selectively disrupting kappa opioid signaling in astroctyes on behavior. ..
  43. Epithelial JNK-TGFb1 Signaling Axis in Airway Remodeling
    Yvonne M W Janssen-Heininger; Fiscal Year: 2013
    ..We will assess the impact of delivery of let-7g pre-miRNA on HDM-induced remodeling. ..
  44. Accessibility Control of Antigen Receptor Gene Assembly
    Eugene M Oltz; Fiscal Year: 2013
    ..We propose studies to address how precursor T lymphocytes activate the T cell receptor beta locus at the earliest stages of thymocyte development to ensure its proper assembly by V(D)J recombination. ..
  45. Cpdm: Cloning a Gene That Regulates Eosinophil Function
    JOHN PAUL SUNDBERG; Fiscal Year: 2013
    ....
  46. Melanocortin Signaling in Depression
    Michael Lutter; Fiscal Year: 2013
    ..The purpose of this research is to investigate the link between mood disorders and feeding and body weight regulation. ..
  47. LOCALIZED REVISION OF EPIGENETIC LANDSCAPES INDUCED BY DNA DOUBLE-STRAND BREAKS
    Barry P Sleckman; Fiscal Year: 2012
    ..We now propose to identify histone modifications that function as intermediates to coordinate the normal repair of DNA-DSBs in mammalian cells. ..
  48. Rho Kinase and Airway Hyperresponsiveness
    Stephanie A Shore; Fiscal Year: 2013
    ..Thus, the ROCK pathway may be an important and still relatively unexplored therapeutic target in asthma. Understanding the role of ROCKs in mouse models of asthma could lead to new strategies for preventing this disease. ..
  49. Modulation of beta-cell PKA activity affects glucose homeostasis
    Barton Wicksteed; Fiscal Year: 2013
    ..It will also reveal potential pitfalls of harnessing this pathway for the treatment of diabetes. ..
  50. THE TEMPORAL AND SPATIAL REGULATION OF BONE ACQUISITION BY SERUM IGF-1
    Shoshana Yakar; Fiscal Year: 2012
    ....
  51. Humanization of hFcRn Mice for Physiological Evaluation of Therapeutic Antibodies
    MICHAEL VAN WILES; Fiscal Year: 2013
    ..We fully expect these models to more accurately reflect human IgG and human albumin biology and, therefore, rapidly advance drug development and FcRn biology. ..
  52. Regulatory architecture of the Androgen Receptor locus in development & evolution
    Philip L Reno; Fiscal Year: 2010
    ..Identifying the mechanisms by which AR expression is regulated may aid in the long-term diagnosis and treatment of these and other human diseases. ..
  53. Conditional Isolation of Fgf23 Activity
    Kenneth E White; Fiscal Year: 2011
    ..These disorders currently have inadequate treatments. We expect that development of an Fgf23 conditional-null animal will reveal new mechanisms involved in phosphate homeostasis, and will provide novel therapeutic targets. ..
  54. TRH REGULATION/BIOSYNTHESIS AND PARAVENTRICULAR NUCLEUS
    RONALD MICHAEL LECHAN; Fiscal Year: 2010
    ....
  55. Transgenic Mouse Models of FUS/TLS-Mediated Amyotrophic Lateral Sclerosis
    Zuoshang Xu; Fiscal Year: 2010
    ..This project will address the urgent need to develop informative mouse models of ALS that will i) accelerate the identification of novel treatment target(s) and ii) enable the testing of new therapeutic strategies to combat ALS. ..
  56. Systematic functional analysis of non-coding sequences in transgenic zebrafish
    Shannon Fisher; Fiscal Year: 2010
    ..Through application of this approach, we aim to establish a paradigm and generate reagents that will aid our understanding of the wealth of information arising out of genome sequencing efforts. ..
  57. Defining the Role of MafA in Islet Beta Cells
    Roland W Stein; Fiscal Year: 2013
    ..The data generated here will provide valuable insight into the transcriptional regulatory mechanisms that will likely be impactful in the production of cellular therapeutics for diabetes treatment. ..
  58. Modeling the KIF5B-RET Fusion Gene of Lung Cancer in Vivo
    Jie Wu; Fiscal Year: 2013
    ..This will provide an important resource for the research community to accelerate the generation of mouse models of newly identified molecular lesions. ..
  59. MOLECULAR PROGRAMMING OF SALIVARY GLAND GENE EXPRESSION
    David K Ann; Fiscal Year: 2013
    ....
  60. Regulation of Cocaine Reward and Reinforcement by MeCP2
    ANNE ELIZABETH WEST; Fiscal Year: 2013
    ..These studies promise to yield significant new insights into the neurobiological mechanisms that impact susceptibility to cocaine addiction. ..
  61. Functional role of RAG2 H3K4me3 interaction in V(D)J recombination
    Marjorie Oettinger; Fiscal Year: 2009
    ..abstract_text> ..
  62. Estrogen signaling transgenic mouse models
    Richard R Behringer; Fiscal Year: 2011
    ..This project will develop novel estrogen receptor transgenic mouse models to activate estrogen-regulated gene expression in different organs to study the diverse physiological and pathological processes controlled by estrogen. ..
  63. PAIRING OF HOMOLOGOUS SEQUENCES IN DROSOPHILA
    KENT GOLIC; Fiscal Year: 2002
    ....
  64. NEW GENE THERAPY FOR CONNECTIVE TISSUE DISEASES
    Eric Kmiec; Fiscal Year: 1999
    ..In this proposal, we will extend our preliminary results to more clinically relevant protocols by attempting to correct mutations of genomic sequences involved in several inherited connective tissue diseases. ..
  65. The Sertoli Cell Product, Doppel, and Male Fertility
    William Wright; Fiscal Year: 2009
    ..Such evidence may open new avenues to the study of male fertility and, thus, to the treatment of the large population of infertile men that live in the United States. ..
  66. Antigenic variation by multiple promoter inversions in Mycoplasma penetrans
    Michael Calcutt; Fiscal Year: 2009
    ..The study of the system of antigenic variation in this organism will both further our understanding of this complex process and provide a platform for the future development of strategies for treatment and prevention. ..
  67. Targeted Manipulation of the Zebrafish Genome through Homologous Recombination
    Brian Ciruna; Fiscal Year: 2010
    ....
  68. Protein Kinase D and Epidermal Structure and Function
    Wendy B Bollag; Fiscal Year: 2010
    ..This research should provide insight into the role of protein kinase D in skin structure and function and allow identification of new targets for the development of drugs to treat human skin diseases. ..
  69. Broad spectrum therapeutics targeting resolvase enzymes
    Frederic D Bushman; Fiscal Year: 2010
    ..and two pieces of equipment will be purchased (a fluorescence plate reader and a -80[unreadable]C freezer) from American sources. advancing the goals of the ARRA. sources, thereby advancing the goals of the ARRA...
  70. REGULATION OF CELL FATE IN MUSCULOSKELETAL DEVELOPMENT
    Barbara Wold; Fiscal Year: 1999
    ..The second goal is to provide a well-controlled and experimentally accessible series of tests for Recombinase mediated lineage tracing in the mouse. ..
  71. Physiologic Role of the Somatotroph IGF-1 Receptor
    Christopher Romero; Fiscal Year: 2009
    ..In the future, this may provide the basis for guidelines for the evaluation and treatment of children with growth disorders. ..
  72. MOUSE CANCER MODELS BY REGULATED INACTIVATION OF TUMOR S
    Eva Lee; Fiscal Year: 2003
    ..These valuable mouse models will be extremely useful for the general community of cancer researchers. ..
  73. Disruption of the SGk1 gene in aldosterone target cells.
    ANIKO NARAY FEJES TOTH; Fiscal Year: 2002
    ..abstract_text> ..