endodeoxyribonucleases

Summary

Summary: A group of enzymes catalyzing the endonucleolytic cleavage of DNA. They include members of EC 3.1.21.-, EC 3.1.22.-, EC 3.1.23.- (DNA RESTRICTION ENZYMES), EC 3.1.24.- (DNA RESTRICTION ENZYMES), and EC 3.1.25.-.

Top Publications

  1. pmc Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection
    Vikram Pattanayak
    Department of Chemistry and Chemical Biology, and Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA
    Nat Methods 8:765-70. 2011
  2. pmc Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing
    Eleni P Mimitou
    Department of Microbiology, Columbia University Medical Center, 701 West 168th Street, New York, New York 10032, USA
    Nature 455:770-4. 2008
  3. pmc A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation
    Jing Pan
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 144:719-31. 2011
  4. ncbi An unbiased genome-wide analysis of zinc-finger nuclease specificity
    Richard Gabriel
    Department of Translational Oncology, National Center for Tumor Diseases NCT and German Cancer Research Center DKFZ, Heidelberg, Germany
    Nat Biotechnol 29:816-23. 2011
  5. pmc Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase
    Kseniya Zakharyevich
    Department of Microbiology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
    Cell 149:334-47. 2012
  6. pmc Bidirectional resection of DNA double-strand breaks by Mre11 and Exo1
    Valerie Garcia
    Genome Damage and Stability Centre, The University of Sussex, Brighton, BN1 9RQ, UK
    Nature 479:241-4. 2011
  7. ncbi Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination
    Silvia Panizza
    Department of Chromosome Biology, Max F Perutz Laboratories, University of Vienna, Dr Bohr Gasse 1, A 1030 Vienna, Austria
    Cell 146:372-83. 2011
  8. pmc BLM helicase ortholog Sgs1 is a central regulator of meiotic recombination intermediate metabolism
    Arnaud De Muyt
    Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 46:43-53. 2012
  9. pmc ATM controls meiotic double-strand-break formation
    Julian Lange
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA
    Nature 479:237-40. 2011
  10. ncbi Enhancing gene targeting with designed zinc finger nucleases
    Marina Bibikova
    Department of Biochemistry, University of Utah School of Medicine, 20 North 1900 East, Salt Lake City, UT 84132 3201, USA
    Science 300:764. 2003

Research Grants

  1. NOVEL HUMAN GENE SPECIFIC REAGENTS FROM HOMING ENDOS
    Raymond Monnat; Fiscal Year: 2005
  2. Checkpoint Signaling and Repair of UV Damage to Human DNA
    Yue Zou; Fiscal Year: 2007
  3. STRUCTURAL STUDIES OF INTRON ENCODED ENDONUCLEASES
    Patrick Van Roey; Fiscal Year: 2001
  4. Postdoctoral Training in Renal Diseases and Hypertension
    BRUCE KONE; Fiscal Year: 2006
  5. Conference Proposal: FASEB Nucleic Acid Enzymes
    Barry Stoddard; Fiscal Year: 2006
  6. Computations of Fold Changes in Evolution of Proteins
    Nick Grishin; Fiscal Year: 2006
  7. A Genetic System Able to Screen for Active DNA Demethylation
    Shuang yong Xu; Fiscal Year: 2006
  8. Mechanisms of Mitotic Recombination
    JEFF JOSEPH SEKELSKY; Fiscal Year: 2010
  9. Targeted gene repair of primary immune deficiencies
    Andrew Scharenberg; Fiscal Year: 2006
  10. DNA Packaging Motors
    Philip Serwer; Fiscal Year: 2005

Detail Information

Publications273 found, 100 shown here

  1. pmc Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection
    Vikram Pattanayak
    Department of Chemistry and Chemical Biology, and Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA
    Nat Methods 8:765-70. 2011
    ..Our findings establish an energy compensation model of ZFN specificity in which excess binding energy contributes to off-target ZFN cleavage and suggest strategies for the improvement of future ZFN design...
  2. pmc Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing
    Eleni P Mimitou
    Department of Microbiology, Columbia University Medical Center, 701 West 168th Street, New York, New York 10032, USA
    Nature 455:770-4. 2008
    ..Second, Exo1 and/or Sgs1 rapidly process this intermediate to generate extensive tracts of single-stranded DNA that serve as substrate for Rad51...
  3. pmc A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation
    Jing Pan
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 144:719-31. 2011
    ..This map illuminates the occurrence of DSBs in repetitive DNA elements, repair of which can lead to chromosomal rearrangements. We also discuss implications for evolutionary dynamics of recombination hot spots...
  4. ncbi An unbiased genome-wide analysis of zinc-finger nuclease specificity
    Richard Gabriel
    Department of Translational Oncology, National Center for Tumor Diseases NCT and German Cancer Research Center DKFZ, Heidelberg, Germany
    Nat Biotechnol 29:816-23. 2011
    ..Comprehensive mapping of ZFN activity in vivo will facilitate the broad application of these reagents in translational research...
  5. pmc Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase
    Kseniya Zakharyevich
    Department of Microbiology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
    Cell 149:334-47. 2012
    ..Thus, Sgs1, Exo1, and MutLγ together define a previously undescribed meiotic JM resolution pathway that produces the majority of crossovers in budding yeast and, by inference, in mammals...
  6. pmc Bidirectional resection of DNA double-strand breaks by Mre11 and Exo1
    Valerie Garcia
    Genome Damage and Stability Centre, The University of Sussex, Brighton, BN1 9RQ, UK
    Nature 479:241-4. 2011
    ..Mre11 exonuclease activity also confers resistance to DNA damage in cycling cells, suggesting that Mre11-catalysed resection may be a general feature of various DNA repair pathways...
  7. ncbi Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination
    Silvia Panizza
    Department of Chromosome Biology, Max F Perutz Laboratories, University of Vienna, Dr Bohr Gasse 1, A 1030 Vienna, Austria
    Cell 146:372-83. 2011
    ..Loss of Rec114, Mer2, and Mei4 binding correlates with loss of DSBs. Our results strongly suggest that hotspot sequences become tethered to axis sites by the DSB machinery prior to DSB formation...
  8. pmc BLM helicase ortholog Sgs1 is a central regulator of meiotic recombination intermediate metabolism
    Arnaud De Muyt
    Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 46:43-53. 2012
    ..We conclude that Sgs1 is a primary regulator of recombination pathway choice during meiosis and suggest a similar function in the mitotic cell cycle...
  9. pmc ATM controls meiotic double-strand-break formation
    Julian Lange
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA
    Nature 479:237-40. 2011
    ..Our findings explain previously puzzling phenotypes of Atm-null mice and provide a molecular basis for the gonadal dysgenesis observed in ataxia telangiectasia, the human syndrome caused by ATM deficiency...
  10. ncbi Enhancing gene targeting with designed zinc finger nucleases
    Marina Bibikova
    Department of Biochemistry, University of Utah School of Medicine, 20 North 1900 East, Salt Lake City, UT 84132 3201, USA
    Science 300:764. 2003
  11. ncbi The mouse Spo11 gene is required for meiotic chromosome synapsis
    P J Romanienko
    Genetics and Biochemistry Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health 20892, Bethesda, MD, USA
    Mol Cell 6:975-87. 2000
    ..We speculate that there is an additional role for Spo11, after it generates DSBs, in synapsis...
  12. pmc Identification and characterization of a family of mammalian methyl-CpG binding proteins
    B Hendrich
    Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, Scotland
    Mol Cell Biol 18:6538-47. 1998
    ..The data demonstrate that MBD2 and MBD4 bind specifically to methyl-CpG in vitro and in vivo and are therefore likely to be mediators of the biological consequences of the methylation signal...
  13. ncbi Synaptonemal complex assembly in C. elegans is dispensable for loading strand-exchange proteins but critical for proper completion of recombination
    MONICA P COLAIACOVO
    Department of Developmental Biology, Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
    Dev Cell 5:463-74. 2003
    ..Our data also suggest that early prophase barriers to utilization of sister chromatids as repair templates do not depend on central region assembly...
  14. ncbi Mechanism and control of meiotic recombination initiation
    S Keeney
    Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, and Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10021, USA
    Curr Top Dev Biol 52:1-53. 2001
    ....
  15. ncbi Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11
    F Baudat
    Cell Biology Program Memorial Sloan Kettering Cancer Center New York, NY 10021, USA
    Mol Cell 6:989-98. 2000
    ..Our results also support the view that mammalian checkpoint responses to meiotic recombination and/or synapsis defects are sexually dimorphic...
  16. pmc Mechanism of Holliday junction resolution by the human GEN1 protein
    Ulrich Rass
    London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts, United Kingdom
    Genes Dev 24:1559-69. 2010
    ..However, the unique feature of GEN1 that distinguishes it from other Rad2/XPG nucleases is its ability to dimerize on HJs. This functional adaptation provides the two symmetrically aligned active sites required for HJ resolution...
  17. ncbi The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements
    Kirill S Lobachev
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Cell 108:183-93. 2002
    ..Our results suggest an additional role for the Mre11 complex in maintaining genome stability...
  18. ncbi The COMPASS subunit Spp1 links histone methylation to initiation of meiotic recombination
    Laurent Acquaviva
    Marseille Cancer Research Center, U1068 Inserm, UMR7258 CNRS, Aix Marseille University, Institut Paoli Calmettes, Marseille 13009, France
    Science 339:215-8. 2013
    ..Thus, by interacting with H3K4me3 and Mer2, Spp1 promotes recruitment of potential meiotic DSB sites to the chromosomal axis, allowing Spo11 cleavage at nearby nucleosome-depleted regions...
  19. pmc Caenorhabditis elegans HIM-18/SLX-4 interacts with SLX-1 and XPF-1 and maintains genomic integrity in the germline by processing recombination intermediates
    Takamune T Saito
    Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Genet 5:e1000735. 2009
    ..elegans BLM homolog. We propose that HIM-18 facilitates processing of HR intermediates resulting from replication fork collapse and programmed meiotic DSBs in the C. elegans germline...
  20. ncbi Highly efficient endogenous human gene correction using designed zinc-finger nucleases
    Fyodor D Urnov
    Sangamo BioSciences, Inc, Pt Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nature 435:646-51. 2005
    ..We observe comparably high frequencies in human T cells, raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease...
  21. pmc The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks
    Katsuhiro Hanada
    Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands
    EMBO J 25:4921-32. 2006
    ..We propose that Mus81-Eme1- and Rad54-mediated homologous recombination are involved in the same DNA replication-dependent ICL repair pathway...
  22. pmc Ku prevents Exo1 and Sgs1-dependent resection of DNA ends in the absence of a functional MRX complex or Sae2
    Eleni P Mimitou
    Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY, USA
    EMBO J 29:3358-69. 2010
    ..Finally, we show that the presence of Ku exacerbates DNA end-processing defects established in the sae2Δ sgs1Δ mutant, leading to its lethality...
  23. ncbi Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage
    S E Lee
    Rosenstiel Center, Department of Biology, Brandeis University, Waltham, Massachusetts 02454 9110, USA
    Cell 94:399-409. 1998
    ..We suggest that escape from the DNA damage-induced G2/M checkpoint depends on the extent of ssDNA created at broken chromosome ends. RPA appears to play a key intermediate step in this adaptation...
  24. pmc Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends
    Zhu Zhu
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Cell 134:981-94. 2008
    ..These results provide important insights into the early steps of DSB repair in eukaryotes...
  25. pmc Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases
    Sarah Baxter
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Nucleic Acids Res 40:7985-8000. 2012
    ..This method will be useful for creating large numbers of chimeric LHEs for genome engineering applications...
  26. pmc Mre11-Rad50-Xrs2 and Sae2 promote 5' strand resection of DNA double-strand breaks
    Matthew L Nicolette
    The Howard Hughes Medical Institute and the Department of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, Texas, USA
    Nat Struct Mol Biol 17:1478-85. 2010
    ..This stimulation is mainly caused by cooperative binding of DNA substrates by Exo1, MRX and Sae2. This work establishes the direct role of MRX and Sae2 in promoting the resection of 5' strands in DNA DSB repair...
  27. pmc DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2
    Petr Cejka
    Department of Microbiology, University of California, Davis, Davis, California 95616 8665, USA
    Nature 467:112-6. 2010
    ..We suggest that Top3-Rmi1 and MRX are important for recruitment of the Sgs1-Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes...
  28. pmc Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination
    Oliver Limbo
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell 28:134-46. 2007
    ..Transcription of ctp1(+) is periodic during the cell cycle, with the onset of its expression coinciding with the start of DNA replication. These data suggest that regulation of Ctp1 underlies cell-cycle control of HR...
  29. ncbi Disjunction of homologous chromosomes in meiosis I depends on proteolytic cleavage of the meiotic cohesin Rec8 by separin
    S B Buonomo
    Research Institute of Molecular Pathology, University of Vienna, Austria
    Cell 103:387-98. 2000
    ..We show here that cleavage of Rec8 by separin at one of two different sites is necessary for the resolution of chiasmata and the disjunction of homologous chromosomes during meiosis...
  30. ncbi SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes
    Marina A Bellani
    Genetics and Biochemistry Branch, NIDDK, NIH, Bethesda, MD 20892, USA
    J Cell Sci 118:3233-45. 2005
    ....
  31. ncbi Endonuclease G regulates budding yeast life and death
    Sabrina Buttner
    Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria
    Mol Cell 25:233-46. 2007
    ..Deletion of NUC1 diminishes apoptotic death when mitochondrial respiration is increased but enhances necrotic death when oxidative phosphorylation is repressed, pointing to dual--lethal and vital--roles for EndoG...
  32. 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...
  33. pmc SLX-1 is required for maintaining genomic integrity and promoting meiotic noncrossovers in the Caenorhabditis elegans germline
    Takamune T Saito
    Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Genet 8:e1002888. 2012
    ..Moreover, we hypothesize that SLX-1 regulates the crossover landscape during meiosis by acting as a noncrossover-promoting factor in a subset of DSBs...
  34. pmc Meganucleases and other tools for targeted genome engineering: perspectives and challenges for gene therapy
    George Silva
    Cellectis Genome Surgery, 102 Avenue Gaston Roussel, Romainville Cedex, France
    Curr Gene Ther 11:11-27. 2011
    ..Here, we review these alternative approaches, with a special emphasis on meganucleases, a family of naturally occurring rare-cutting endonucleases, and speculate on their current and future potential...
  35. pmc Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks
    Eun Yong Shim
    Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
    EMBO J 29:3370-80. 2010
    ..However, Mre11 nuclease activity is essential for resection in the absence of extensive resection enzymes. The results provide new insights into how MRX catalyses end resection and recombination initiation...
  36. pmc Endonucleolytic processing of covalent protein-linked DNA double-strand breaks
    Matthew J Neale
    Molecular Biology Programs, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 436:1053-7. 2005
    ..Our findings suggest a general mechanism for repair of protein-linked DSBs...
  37. ncbi A DNA damage response pathway controlled by Tel1 and the Mre11 complex
    T Usui
    Department of Biology, Graduate School of Science, Osaka University, Toyonaka, 560 0043, Osaka, Japan
    Mol Cell 7:1255-66. 2001
    ..These findings demonstrate that the diverse functions of the Mre11 complex in the cellular DNA damage response are conserved in mammals and yeast...
  38. pmc The nuclease activity of Mre11 is required for meiosis but not for mating type switching, end joining, or telomere maintenance
    S Moreau
    Institute of Cancer Research and Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Mol Cell Biol 19:556-66. 1999
    ..We propose that in mitotic cells DSBs can be processed by other nucleases that are partially redundant with Mre11, but these activities are unable to process Spo11-bound DSBs in meiotic cells...
  39. pmc The Mre11:Rad50 structure shows an ATP-dependent molecular clamp in DNA double-strand break repair
    Katja Lammens
    Center for Integrated Protein Science Munich, Ludwig Maximilians University Munich, Feodor Lynen Strasse 25, 81377 Munich, Germany
    Cell 145:54-66. 2011
    ..The results suggest that MR is an ATP-controlled transient molecular clamp at DNA double-strand breaks...
  40. pmc The axial element protein HTP-3 promotes cohesin loading and meiotic axis assembly in C. elegans to implement the meiotic program of chromosome segregation
    Aaron F Severson
    Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA
    Genes Dev 23:1763-78. 2009
    ..Premature equational sister separation in rec8 mutants of other organisms suggests the involvement of multiple REC-8 paralogs, which may have masked a conserved requirement for cohesin in AE assembly...
  41. ncbi DNA damage signaling recruits the Rtt107-Slx4 scaffolds via Dpb11 to mediate replication stress response
    Patrice Y Ohouo
    Graduate Program in Biochemistry, Molecular and Cell Biology, Weill Institute for Cell and Molecular Biology, Cornell University, 339 Weill Hall, Ithaca, New York 14853 7202, USA
    Mol Cell 39:300-6. 2010
    ..Our results unveil how Mec1 regulates the Slx4 and Rtt107 scaffolds and establish a mechanistic link between DNA damage signaling and fork repair...
  42. pmc Structural, functional and evolutionary relationships between homing endonucleases and proteins from their host organisms
    Gregory K Taylor
    Graduate Program in Molecular and Cellular Biology, University of Washington and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N A3 025, Seattle, WA 90109, USA
    Nucleic Acids Res 40:5189-200. 2012
    ..This review summarizes the results of structural studies of HEs and corresponding proteins from host organisms that have illustrated the manner in which these factors are related...
  43. ncbi A synaptonemal complex protein promotes homology-independent centromere coupling
    Tomomi Tsubouchi
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Science 308:870-3. 2005
    ..Regions of synaptonemal complex assembled early in meiosis are often centromere-associated. We propose that centromere coupling facilitates homolog pairing and promotes synapsis initiation...
  44. pmc Functional interplay of the Mre11 nuclease and Ku in the response to replication-associated DNA damage
    Steven S Foster
    Laboratory of Chromosome Biology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, RRL 901C, New York, NY 10021, USA
    Mol Cell Biol 31:4379-89. 2011
    ..Collectively, the data define a nonhomologous end joining (NHEJ)-independent, S-phase-specific function of the Ku heterodimer...
  45. pmc Creating highly specific nucleases by fusion of active restriction endonucleases and catalytically inactive homing endonucleases
    Ines Fonfara
    Institut fur Biochemie, Justus Liebig Universitat Giessen, Heinrich Buff Ring 58, D 35392, Giessen, Germany
    Nucleic Acids Res 40:847-60. 2012
    ....
  46. pmc Single-strand nicks induce homologous recombination with less toxicity than double-strand breaks using an AAV vector template
    Michael J Metzger
    Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Nucleic Acids Res 39:926-35. 2011
    ....
  47. pmc Crystal structure of the Mus81-Eme1 complex
    Jeong Ho Chang
    National Creative Initiatives for Structural Biology and Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbook 790 784, South Korea
    Genes Dev 22:1093-106. 2008
    ....
  48. ncbi Systematic genetic analysis with ordered arrays of yeast deletion mutants
    A H Tong
    Banting and Best Department of Medical Research, University of Toronto, Toronto ON, Canada M5G 1L6
    Science 294:2364-8. 2001
    ..Systematic application of this approach should produce a global map of gene function...
  49. ncbi Uptake of transforming DNA in Gram-positive bacteria: a view from Streptococcus pneumoniae
    Mathieu Berge
    Laboratoire de Microbiologie et Genetique Moleculaire, UMR 5100 CNRS Université Paul, Sabatier, 118 route de Narbonne, 31062 Toulouse Cedex, France
    Mol Microbiol 45:411-21. 2002
    ..Finally, inactivation of dprA had no effect on the internalization of DNA, indicating that DprA is required at a later stage in transformation...
  50. ncbi Endonuclease G is an apoptotic DNase when released from mitochondria
    L Y Li
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75390, USA
    Nature 412:95-9. 2001
    ..Once released from mitochondria, endoG cleaves chromatin DNA into nucleosomal fragments independently of caspases. Therefore, endoG represents a caspase-independent apoptotic pathway initiated from the mitochondria...
  51. 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...
  52. pmc The generation of proper constitutive G-tails on yeast telomeres is dependent on the MRX complex
    Michel Larrivée
    Departement De Microbiologie et Infectiologie, Groupe ARN RNA Group, Faculte de Medecine, Universite de Sherbrooke, Sherbrooke, J1H 5N4 Canada
    Genes Dev 18:1391-6. 2004
    ..Thus, G-tails are present on yeast chromosomes throughout the cell cycle and the MRX complex is required for their normal establishment...
  53. ncbi The junction-resolving enzymes
    D M Lilley
    CRC Nucleic Acid Structure Research Group, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, UK
    Nat Rev Mol Cell Biol 2:433-43. 2001
    ..This poses an intriguing challenge in molecular recognition on a relatively large scale...
  54. ncbi Human MUS81 complexes stimulate flap endonuclease 1
    Yong Keol Shin
    Department of Biological Sciences, Center for DNA Replication and Genome Instability, Korea Advanced Institute of Science and Technology, Daejeon, Korea
    FEBS J 279:2412-30. 2012
    ..Thus, the mammalian MUS81 complexes and FEN1 collaborate to remove the various flap structures that arise during many DNA transactions, including Okazaki fragment processing...
  55. pmc Distinct roles of two separable in vitro activities of yeast Mre11 in mitotic and meiotic recombination
    M Furuse
    Cellular and Molecular Biology Laboratory, The Institute of Physical and Chemical Research RIKEN, Wako Shi, Saitama 351 0198, Japan
    EMBO J 17:6412-25. 1998
    ....
  56. ncbi A central coupler for recombination initiation linking chromosome architecture to S phase checkpoint
    Tomoichiro Miyoshi
    Department of Life Sciences, The University of Tokyo, Komaba 3 8 1, Meguro ku, Tokyo 153 8902, Japan
    Mol Cell 47:722-33. 2012
    ..These data lead us to propose a mechanism by which Mde2 functions as a recombination initiation mediator to tether axes and loops, in liaison with the meiotic replication checkpoint...
  57. pmc Crystal structure of the Mre11-Rad50-ATPγS complex: understanding the interplay between Mre11 and Rad50
    Hye Seong Lim
    Department of Life Science, Pohang University of Science and Technology, Pohang, South Korea
    Genes Dev 25:1091-104. 2011
    ..Our structural and biochemical data provide insights into understanding the interplay between Mre11 and Rad50 to facilitate efficient DNA damage repair...
  58. pmc EENdb: a database and knowledge base of ZFNs and TALENs for endonuclease engineering
    An Xiao
    Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, College of Life Sciences, Peking University, Beijing 100871, China
    Nucleic Acids Res 41:D415-22. 2013
    ..These studies may help to extract in-depth properties and common rules regarding ZFN or TALEN efficiency through comparison of the known ZFNs or TALENs...
  59. pmc The Rad50 coiled-coil domain is indispensable for Mre11 complex functions
    Marcel Hohl
    Laboratory of Chromosome Biology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Nat Struct Mol Biol 18:1124-31. 2011
    ..These data show that functions of Mre11 complex are integrated by the coiled coils of Rad50...
  60. pmc Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants
    Monica Di Giacomo
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center and Weill Graduate School of Medical Sciences of Cornell University, 1275 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 102:737-42. 2005
    ..The absence of ATM caused defects in folliculogenesis that were similar to those in Dmc1 mutants and that could be suppressed by Spo11 mutation, implying that oocyte death in Atm-deficient animals is a response to defective DSB repair...
  61. pmc Three structure-selective endonucleases are essential in the absence of BLM helicase in Drosophila
    Sabrina L Andersen
    Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
    PLoS Genet 7:e1002315. 2011
    ..Our studies of synthetic lethality provide insights into the multiple functions of DmBLM and how various endonucleases may function when DmBLM is absent...
  62. pmc DNA nicks promote efficient and safe targeted gene correction
    Luther Davis
    Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America
    PLoS ONE 6:e23981. 2011
    ..42±0.03%, respectively). Thus nicks initiate efficient gene correction, with limited local mutagenesis. These results have clear therapeutic implications, and should inform future design of meganucleases for targeted gene correction...
  63. pmc DNA bending and a flip-out mechanism for base excision by the helix-hairpin-helix DNA glycosylase, Escherichia coli AlkA
    T Hollis
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    EMBO J 19:758-66. 2000
    ..The structure of the AlkA-DNA complex offers the first glimpse of a helix-hairpin-helix (HhH) glycosylase complexed to DNA. Modeling studies suggest that other HhH glycosylases can bind to DNA in a similar manner...
  64. pmc Cdc7-dependent phosphorylation of Mer2 facilitates initiation of yeast meiotic recombination
    Hiroyuki Sasanuma
    Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba 3 8 1, Meguro ku, Tokyo 153 8902, Japan
    Genes Dev 22:398-410. 2008
    ..We thus propose that Cdc7, in concert with CDK, regulates Spo11 loading to DSB sites via Mer2 phosphorylation...
  65. ncbi Mus81-Eme1 are essential components of a Holliday junction resolvase
    M N Boddy
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 107:537-48. 2001
    ..The mus81 meiotic defect is rescued by expression of a bacterial Holliday junction resolvase. These findings constitute strong evidence that Mus81 and Eme1 are subunits of a nuclear Holliday junction resolvase...
  66. pmc Distinct properties of the XY pseudoautosomal region crucial for male meiosis
    Liisa Kauppi
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Science 331:916-20. 2011
    ..Our findings uncover specific mechanisms that surmount the unique challenges of X-Y recombination...
  67. pmc Cleavage mechanism of human Mus81-Eme1 acting on Holliday-junction structures
    Ewan R Taylor
    Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 105:3757-62. 2008
    ....
  68. pmc ABC ATPase signature helices in Rad50 link nucleotide state to Mre11 interface for DNA repair
    Gareth J Williams
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA
    Nat Struct Mol Biol 18:423-31. 2011
    ....
  69. pmc Saccharomyces cerevisiae checkpoint genes MEC1, RAD17 and RAD24 are required for normal meiotic recombination partner choice
    J M Grushcow
    Department of Radiation, University of Chicago, Chicago, Illinois 60637, USA
    Genetics 153:607-20. 1999
    ..These observations support the suggestion that MEC1, RAD17, and RAD24, in addition to their proposed monitoring function, act to promote normal meiotic recombination...
  70. pmc Progression of meiotic DNA replication is modulated by interchromosomal interaction proteins, negatively by Spo11p and positively by Rec8p
    R S Cha
    Department of Molecular Biology, Harvard University, Cambridge, Massachusetts 02138 USA
    Genes Dev 14:493-503. 2000
    ..Roles for Rec8 and/or Spo11 in progression through other stages of meiosis are also revealed...
  71. ncbi Homing endonucleases: from basics to therapeutic applications
    Maria J Marcaida
    Macromolecular Crystallography Group, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre CNIO, c Melchor Fdez Almagro 3, 28029 Madrid, Spain
    Cell Mol Life Sci 67:727-48. 2010
    ..The use of tailored HEs opens up new possibilities for gene therapy in patients with monogenic diseases that can be treated ex vivo. This review provides an overview of recent advances in this field...
  72. pmc Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences
    Jia Lin Ma
    Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245, USA
    Mol Cell Biol 23:8820-8. 2003
    ..The increased gamma ray sensitivity of rad1Delta rad52Delta yku70Delta strains compared to rad52Delta yku70Delta strains suggests that MMEJ also contributes to the repair of DSBs induced by ionizing radiation...
  73. ncbi Holliday junction resolvases encoded by homologous rusA genes in Escherichia coli K-12 and phage 82
    A A Mahdi
    Department of Genetics, University of Nottingham Queens Medical Centre, UK
    J Mol Biol 257:561-73. 1996
    ..Multicopy plasmids expressing RusA alone make ruvA, ruvB, and ruvC mutants resistant to UV light. Suppression depends critically on RecG...
  74. ncbi Spp1, a member of the Set1 Complex, promotes meiotic DSB formation in promoters by tethering histone H3K4 methylation sites to chromosome axes
    Vérane Sommermeyer
    Institut Curie, Centre de Recherche, 75248 Paris, France
    Mol Cell 49:43-54. 2013
    ..This paper provides the molecular mechanism linking DSB sequences to chromosome axes and explains why H3K4 methylation is important for meiotic recombination...
  75. pmc Mitochondrial release of AIF and EndoG requires caspase activation downstream of Bax/Bak-mediated permeabilization
    Damien Arnoult
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 22:4385-99. 2003
    ..Thus EndoG and AIF seem to define a 'caspase-dependent' mitochondria-initiated apoptotic DNA degradation pathway that is conserved between mammals and nematodes...
  76. pmc The Mre11 protein interacts with both Rad50 and the HerA bipolar helicase and is recruited to DNA following gamma irradiation in the archaeon Sulfolobus acidocaldarius
    Achim Quaiser
    Univ Paris Sud, Institut de Genetique et Microbiologie, CNRS UMR 8621, Batiment 409, F 91405 Orsay cedex, France
    BMC Mol Biol 9:25. 2008
    ..Since genetic tools for hyperthermophilic archaea are just emerging, we utilized immuno-detection approaches to get the first in vivo data on the role(s) of these proteins in the hyperthermophilic crenarchaeon Sulfolobus acidocaldarius...
  77. pmc Gamma radiation increases endonuclease-dependent L1 retrotransposition in a cultured cell assay
    Evan A Farkash
    Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Nucleic Acids Res 34:1196-204. 2006
    ..The mobilization of L1 in irradiated cells potentially contributes to genomic instability and could be a driving force for secondary mutations in patients undergoing radiation therapy...
  78. pmc DNA interstrand crosslink repair during G1 involves nucleotide excision repair and DNA polymerase zeta
    Sovan Sarkar
    Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
    EMBO J 25:1285-94. 2006
    ..We show that this combination of NER and TLS is the only pathway of ICL repair available to the cell in G1 phase and is essential for viability in the presence of DNA crosslinks...
  79. pmc Yeast nucleotide excision repair proteins Rad2 and Rad4 interact with RNA polymerase II basal transcription factor b (TFIIH)
    A J Bardwell
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235
    Mol Cell Biol 14:3569-76. 1994
    ..Furthermore, the loading of factor b (or such intermediates) onto promoters during transcription initiation provides a mechanism for the preferential targeting of repair proteins to actively transcribing genes...
  80. ncbi S. cerevisiae Tel1p and Mre11p are required for normal levels of Est1p and Est2p telomere association
    Lara K Goudsouzian
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    Mol Cell 24:603-10. 2006
    ..These data argue that Mre11p and Tel1p affect telomere length by promoting telomerase recruitment to telomeres, whereas Mec1p has only a minor role in telomerase recruitment in a TEL1 cell...
  81. pmc Distinct roles of Mus81, Yen1, Slx1-Slx4, and Rad1 nucleases in the repair of replication-born double-strand breaks by sister chromatid exchange
    Sandra Muñoz-Galván
    Centro Andaluz de Biologia Molecular y Medicina Regenerativa, Universidad de Sevilla CSIC, Seville, Spain
    Mol Cell Biol 32:1592-603. 2012
    ..These unique effects, which have not been detected in other studies unless double mutant combinations were used, indicate the formation of distinct alternatives for the repair of replication-born DSBs that require specific SSEs...
  82. pmc Rec8 guides canonical Spo11 distribution along yeast meiotic chromosomes
    Kazuto Kugou
    Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153 8902, Japan
    Mol Biol Cell 20:3064-76. 2009
    ..These observations suggest that Rec8 would prearrange the distribution of Spo11 along chromosomes and will provide clues to understanding temporal and spatial regulation of DSB formation...
  83. pmc Divalent metal ion differentially regulates the sequential nicking reactions of the GIY-YIG homing endonuclease I-BmoI
    Benjamin P Kleinstiver
    Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada
    PLoS ONE 6:e23804. 2011
    ..Collectively, our data implies mechanistic roles for divalent metal ion and substrate bases, suggesting that divalent metal ion facilitates the re-positioning of the GIY-YIG nuclease domain between sequential nicking reactions...
  84. pmc Activity, specificity and structure of I-Bth0305I: a representative of a new homing endonuclease family
    Gregory K Taylor
    Graduate Program in Molecular and Cellular Biology and the Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA
    Nucleic Acids Res 39:9705-19. 2011
    ..The domain architecture and DNA recognition profile displayed by I-Bth0305I, which is the prototype of a homing lineage that we term the 'EDxHD' family, are distinct from previously characterized homing endonucleases...
  85. pmc Sae2 is an endonuclease that processes hairpin DNA cooperatively with the Mre11/Rad50/Xrs2 complex
    Bettina M Lengsfeld
    Department of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA
    Mol Cell 28:638-51. 2007
    ....
  86. ncbi Genetic and biochemical characterization of MbeA, the relaxase involved in plasmid ColE1 conjugative mobilization
    Athanasia Varsaki
    Sector of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 451 10 Ioannina, Greece
    Mol Microbiol 48:481-93. 2003
    ..Thus, MbeA is a variant of the common relaxase theme with a HEN signature motif, which has to be added to the canonical three histidine motif of previously reported relaxases...
  87. pmc ATP driven structural changes of the bacterial Mre11:Rad50 catalytic head complex
    Carolin Möckel
    Gene Center and Department of Biochemistry, Ludwig Maximilians University Munich, Feodor Lynen Strasse 25, 81377, Munich, Germany
    Nucleic Acids Res 40:914-27. 2012
    ..Our results suggest a possible mechanism for ATP-dependent DNA tethering and DSB processing by MR...
  88. ncbi Adaptation of intronic homing endonuclease for successful horizontal transmission
    Sayuri Kurokawa
    Graduate School of Engineering, Department of Environmental Systems Engineering, Kochi University of Technology KUT, Kochi, Japan
    FEBS J 272:2487-96. 2005
    ....
  89. ncbi Genetic and structural characterization of endA. A membrane-bound nuclease required for transformation of Streptococcus pneumoniae
    A Puyet
    Department of Biology, Brookhaven National Laboratory, Upton, NY 11973
    J Mol Biol 213:727-38. 1990
    ..Neither of these upstream genes, nor the downstream gene, are essential for either cell viability or transformability...
  90. ncbi Atomic structure of the Serratia marcescens endonuclease at 1.1 A resolution and the enzyme reaction mechanism
    S V Shlyapnikov
    Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str 32, Moscow 117984, Russia
    Acta Crystallogr D Biol Crystallogr 56:567-72. 2000
    ..marcescens nuclease structure, the functional characteristics of the natural and mutational forms of the enzyme and consideration of its structural analogy with homing endo-nuclease I-PpoI...
  91. ncbi Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents
    Krishna Kurthkoti
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India
    Microbiology 154:2776-85. 2008
    ..Taken together with previous observations on NER-deficient M. tuberculosis, these results suggest that NER is an important DNA repair pathway in mycobacteria...
  92. ncbi Nucleases of the metallo-beta-lactamase family and their role in DNA and RNA metabolism
    Zbigniew Dominski
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Crit Rev Biochem Mol Biol 42:67-93. 2007
    ..This article reviews the cellular roles of nucleases of the metallo-beta-lactamase family and the recent advances in studying these proteins...
  93. pmc The hSNM1 protein is a DNA 5'-exonuclease
    James Hejna
    Oregon Health and Science University, Department of Molecular and Medical Genetics, 3181 SW Sam Jackson Park Road, Mail Code L103, Portland, OR 97239 3098, USA
    Nucleic Acids Res 35:6115-23. 2007
    ..The exonuclease activity requires the conserved beta-lactamase domain; site-directed mutagenesis of a conserved aspartate inactivates the exonuclease...
  94. pmc Stimulation of homology-directed gene targeting at an endogenous human locus by a nicking endonuclease
    Gijsbert P van Nierop
    Virus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands
    Nucleic Acids Res 37:5725-36. 2009
    ..Finally, harnessing the cellular HR pathway through Rep-mediated nicking expands the range of strategies that make use of AAV elements to bring about stable genetic modification of human cells...
  95. pmc Mre11 nuclease activity and Ctp1 regulate Chk1 activation by Rad3ATR and Tel1ATM checkpoint kinases at double-strand breaks
    Oliver Limbo
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Mol Cell Biol 31:573-83. 2011
    ....
  96. pmc Synapsis-dependent and -independent mechanisms stabilize homolog pairing during meiotic prophase in C. elegans
    Amy J MacQueen
    Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305 5329, USA
    Genes Dev 16:2428-42. 2002
    ....
  97. ncbi Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA
    Hideyuki Yoshida
    Department of Genetics, Osaka University Medical School, 2 2 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Immunol 6:49-56. 2005
    ....
  98. pmc BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures
    Y Wang
    Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:927-39. 2000
    ..Collectively, these results suggest that BRCA1 may function as a coordinator of multiple activities required for maintenance of genomic integrity during the process of DNA replication and point to a central role for BRCA1 in DNA repair...
  99. ncbi Investigation of the substrate spectrum of the human mismatch-specific DNA N-glycosylase MED1 (MBD4): fundamental role of the catalytic domain
    F Petronzelli
    Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
    J Cell Physiol 185:473-80. 2000
    ..This suggests that the catalytic domain is fundamental, and the 5-methylcytosine binding domain dispensable, in determining the substrate spectrum of MED1...
  100. pmc Structural basis for MutH activation in E.coli mismatch repair and relationship of MutH to restriction endonucleases
    C Ban
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 17:1526-34. 1998
    ..With sequence homology to Sau3AI and structural similarity to PvuII endonuclease, MutH is clearly related to these enzymes by divergent evolution, and this suggests that type II restriction endonucleases evolved from a common ancestor...
  101. 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'...

Research Grants65

  1. NOVEL HUMAN GENE SPECIFIC REAGENTS FROM HOMING ENDOS
    Raymond Monnat; Fiscal Year: 2005
    ..The availability of human GSR's may also allow modification of altered human genes responsible for specific diseases or genes of pathogenic microorganisms including bacteria and viruses, parasites, etc. ..
  2. Checkpoint Signaling and Repair of UV Damage to Human DNA
    Yue Zou; Fiscal Year: 2007
    ..abstract_text> ..
  3. STRUCTURAL STUDIES OF INTRON ENCODED ENDONUCLEASES
    Patrick Van Roey; Fiscal Year: 2001
    ..This will allow the comparison of representative examples of the two classes of enzymes that, although otherwise unrelated, carry out the same biological function. ..
  4. Postdoctoral Training in Renal Diseases and Hypertension
    BRUCE KONE; Fiscal Year: 2006
    ..It is the goal of the Program that its graduates will contribute to a new generation of academic nephrologists and renal investigators equipped to address the challenging problems in renal diseases and hypertension ..
  5. Conference Proposal: FASEB Nucleic Acid Enzymes
    Barry Stoddard; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  6. Computations of Fold Changes in Evolution of Proteins
    Nick Grishin; Fiscal Year: 2006
    ..Finally, we will perform in silico evolution of model proteins under functional constraints and compare the results to those deduced from the analysis of natural sequences and structures. ..
  7. A Genetic System Able to Screen for Active DNA Demethylation
    Shuang yong Xu; Fiscal Year: 2006
    ..In addition, knowledge of the mechanism of demethylation could be crucial in converting fully differentiated adult stem cells into totipotent stem cells. [unreadable] [unreadable] [unreadable]..
  8. Mechanisms of Mitotic Recombination
    JEFF JOSEPH SEKELSKY; Fiscal Year: 2010
    ..These studies will enhance our understanding of mechanisms of mitotic crossing over and the role that the important tumor suppressor protein BLM plays in preventing mitotic crossing over. ..
  9. Targeted gene repair of primary immune deficiencies
    Andrew Scharenberg; Fiscal Year: 2006
    ..Overall, the work proposed here will build a foundation of materials and experience for the development of LHE's as general tools for targeted gene therapy of human primary immune deficiencies. ..
  10. DNA Packaging Motors
    Philip Serwer; Fiscal Year: 2005
    ..Analysis of bacteriophage DNA packaging motors is expected to provide a basis for understanding the role of motors in disease, especially disease caused by a virus that has a DNA packaging motor. ..
  11. Engineering DNA nicking endonucleases
    Shuang yong Xu; Fiscal Year: 2006
    ..Under Phase II funding, this isothermal amplification method (NEMDA) will be optimized and the sensitivity will be improved. Finally, we will investigate the potential of NEMDA for detections of pathogens and its use in bio-prospecting. ..
  12. Cytochrome P450 in Reperfusion Injury
    Roberta Gottlieb; Fiscal Year: 2007
    ..This proposal identifies cytochrome P450 monooxygenases as a previously underestimated factor in myocardial reperfusion injury, and establishes the basis for a novel therapeutic approach [unreadable] [unreadable]..
  13. DNA Mismatch and Double-Strand Break Repair
    Martin G Marinus; Fiscal Year: 2010
    ..It also impacts the mechanism by which pathogenic bacteria become resistant to antibiotics and how this resistance is disseminated. ..
  14. INTEGRATED STUDY OF MUSCULOSKELETAL LOSS AND RESTORATION
    Esther E Dupont Versteegden; Fiscal Year: 2010
    ..Identifying these common pathways influencing muscle and bone integrity could lead to putative targets for pharmacologic or therapeutic interventions. ..
  15. Engineering enzymes for anti-tumor suicide gene therapy
    Barry L Stoddard; Fiscal Year: 2010
    ..Our hypothesis is that decitabine should ultimately couple with engineered enzyme variants to yield improvements in the performance of dCK, due to the lack of this activity in non-cancerous tissues. ..
  16. Regulation of H/K-ATPase in Kidney and Colon
    BRUCE KONE; Fiscal Year: 2009
    ..abstract_text> ..
  17. Combined Methods for Protein-Structure Prediction
    Kevin Karplus; Fiscal Year: 2007
    ....
  18. Regulation of L1 retrotransposition
    Eline Luning Prak; Fiscal Year: 2008
    ..A better understanding of how L1 retrotransposition is regulated should yield important insights into L1 biology, mechanism and the potential of L1s to contribute to genomic instability in cancer. ..
  19. Genetic Recombination and Chromosome Rearrangements
    LORRAINE SYMINGTON; Fiscal Year: 2007
    ..Much of the conference will be devoted to topics of concern both to the National Cancer Institute and to the Institute of Environmental and Health Sciences. [unreadable] [unreadable] [unreadable] [unreadable]..
  20. HUMAN OXIDATION RESISTANCE GENES
    Michael Volkert; Fiscal Year: 2007
    ..abstract_text> ..
  21. DNA Damage Clusters: Repair in Mammalian Cells
    Betsy Sutherland; Fiscal Year: 2004
    ..Further, knowledge of conditions affecting formation of clustered damages, and cellular paths for dealing with them could allow the design of more effective radiation therapies. ..
  22. Copy number control of the yeast plasmid
    Makkuni Jayaram; Fiscal Year: 2004
    ..abstract_text> ..
  23. FUNCTION AND REGULATION OF THE E COLI AIDB GENES
    Michael Volkert; Fiscal Year: 2002
    ..During the proposed funding period, I propose to characterize this factor further by genetic and biochemical means and to compare its induction mechanism with that of meAda. ..
  24. Assembly Visualized Routine Flourescence Microscopy
    Philip Serwer; Fiscal Year: 2008
    ..Applications are anticipated in the analysis of the assembly of disease-causing viruses and determining pathways of oncogenesis. ..
  25. RETROTRANSPOSITION IN L1 TRANSGENIC MICE
    Eline Luning Prak; Fiscal Year: 2004
    ..abstract_text> ..
  26. ANALYSIS OF B-CELL RECEPTOR CALCIUM SIGNALING
    Andrew Scharenberg; Fiscal Year: 2004
    ..abstract_text> ..
  27. SCLERODERMA LUNG STUDY
    Maureen Mayes; Fiscal Year: 2003
    ..abstract_text> ..
  28. OXYGEN INDUCED DNA DAMAGE, MUTATIONS AND CANCER
    LAWRENCE LOEB; Fiscal Year: 2003
    ..Even a modest, 2-fold, decrease could increase the latent period before disease is manifested clinically and thus reduce cancer mortality. ..
  29. Genetic Recombination/Genomic Rearrangements Conference
    LORRAINE SYMINGTON; Fiscal Year: 2005
    ..abstract_text> ..
  30. ROLE OF THE LCR IN HUMAN BETA-GLOBIN GENE REGULATION
    KENNETH PETERSON; Fiscal Year: 2001
    ..Specific Aim 3 will test the role of the LCR sequences in LCR complex formation and globin gene regulation using transgenic mice containing mutant beta-globin loci by applying FRET. ..
  31. DNA REPAIR DEFECT IN FANCONI ANEMIA, GROUP A
    MURIEL LAMBERT; Fiscal Year: 2008
    ....
  32. Apoptosis in recombination-deficient meiocytes
    Francesca Cole; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  33. Chimeric Nucleases for Gene Targeting in Drosophila
    Dana Carroll; Fiscal Year: 2003
    ..To test the generality of the method, it will be applied to a second Drosophila locus, the rosy (ry) gene. ..
  34. Bid-Mediated Cytochrome c Release from Mitochondria
    Roberta Gottlieb; Fiscal Year: 2007
    ..These studies will elucidate the molecular mechanism by which BH3-only proteins cause the release of cytochrome c from mitochondria. [unreadable] [unreadable]..
  35. BRAIN TISSUE RESOURCE FOR NEUROPSYCHIATRIC RESEARCH
    Francine Benes; Fiscal Year: 2002
    ..Over the next five years, all of these changes will enhance the "brain bank" in its role as a vital national resource. ..
  36. Mechanisms of Double-strand Break Repair in Yeast
    LORRAINE SYMINGTON; Fiscal Year: 2009
    ..The last aim includes in vitro studies to identify preferred DNA substrates for Rad55:Rad57 binding and stabilization of the Rad51 nucleoprotein by Rad55:Rad57 in the presence or absence of Srs2. ..
  37. CORTICOLIMBIC SYSTEM AND SCHIZOPHRENIA
    Francine Benes; Fiscal Year: 2002
    ....
  38. The Werner Syndrome Protein in DNA Replication, Mutagenesis and Genomic Stability
    Lawrence A Loeb; Fiscal Year: 2010
    ..All of the procedures have been established and are ongoing in our laboratory and can be completed within two years. ..
  39. MECHANISMS OF SITE-SPECIFIC RECOMBINATION
    Makkuni Jayaram; Fiscal Year: 2009
    ..Finally, they will set the stage for analyzing recombination in the context of high-order chromatin and native 2 micron circle physiology. ..
  40. NEUTROPHINS AND RETINAL DEVELOPMENT
    Janet Sparrow; Fiscal Year: 2001
    ..The use of neurotrophins in conjunction with gene therapy or transplantation may also have potential for reversing retinal degenerative changes and lead to the restoration of vision. ..
  41. CREATING MUTANT ENZYMES FOR GENE THERAPY OF CANCER
    LAWRENCE LOEB; Fiscal Year: 2007
    ..abstract_text> ..
  42. 12th International Workshop on Ataxia-Telangiectasia and ATM
    Richard Gatti; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  43. Nucleosomes Modulate DNA Interstrand Crosslink Repair
    MURIEL LAMBERT; Fiscal Year: 2005
    ..abstract_text> ..
  44. Structural studies of blood coagulation proteins
    Barry Stoddard; Fiscal Year: 2006
    ..The third specific aim for this project is to determine the structure of the N-terminal, D'-D3 domain from von Willebrand Factor, alone and/or in complex with factor VIII heterodimer. ..
  45. Stimulating Gene Targeting with Zinc Finger Nucleases
    Dana Carroll; Fiscal Year: 2004
    ..To demonstrate the generality of this approach to gene targeting, it will be applied to another mouse locus, the Rpo2-1 gene. ..
  46. Cloning and Engineering of Nicking enzymes
    Shuang yong Xu; Fiscal Year: 2004
    ..abstract_text> ..
  47. A universal DNA endonuclease
    Shuang yong Xu; Fiscal Year: 2005
    ..For isothermal applications of the universal nuclease at 50oC-70oC, the nuclease domain will be derived from thermophilic endonucleases. ..
  48. DNA Repair and Mutagenesis in S cerevisiae
    Elaine Sia; Fiscal Year: 2005
    ..The experiments in this proposal are aimed at understanding the processes of mutagenesis and repair of mitochondrial DNA in yeast, however, these studies may lead to insights into similar processes in human mitochondrial DNA. ..
  49. Environmental Mutagen Society, 34th Annual Meeting
    LAWRENCE LOEB; Fiscal Year: 2003
    ..Awards will be made to US speakers whose major area of interest is in carcinogenesis. ..
  50. Enhanced Capillary DNA Sequencing
    Philip Serwer; Fiscal Year: 2004
    ..Each adaptation will help solve a current genomic problem, for example, either closing of a partially assembled genome sequence or performing high accuracy analysis of mutations. ..
  51. ANTITUMOR DRUGS AND INHIBITION OF INITIATION OF DNA REPL
    WILLIAM BURHANS; Fiscal Year: 2003
    ..This project will explore these possibilities with a combined genetic and biochemical analysis of the effects of adozelesin and related drugs on initiation of DNA replication in mammalian cells. ..
  52. TRPM2 HTS Screening Assay Development(RMI)
    Andrew Scharenberg; Fiscal Year: 2005
    ..Using the 96 well plate format, we will also evaluate the overall method's properties and suitability for HTS using a library of compounds of known bioactivity. ..
  53. A Multicomponent Anthrax Vaccine using Phage T4 Display
    VENIGALLA RAO; Fiscal Year: 2007
    ..The duration of protection as well as pathological changes will be assessed. ..
  54. CORTICOLIMBIC ABNORMALITIES IN SCHIZOPHRENIC BRAIN
    Francine Benes; Fiscal Year: 2001
    ....
  55. Improving Phenylbutyrate-based Anticancer Therapy
    ASHOK BHAGWAT; Fiscal Year: 2005
    ..This work will create the tools necessary for the monitoring of tumor cells in live animals when they are treated with PB as part of combination chemotherapy. ..
  56. LETHAL MUTAGENESIS OF HIV BY DEOXYNUCLEOSIDE ANALOGS
    LAWRENCE LOEB; Fiscal Year: 2002
    ....
  57. Impaired Regulation of Muscle size with Aging
    ESTHER DUPONT VERSTEEGDEN; Fiscal Year: 2002
    ..Also, potential regulatory pathways and molecules involved in control of muscle size will be determined. ..
  58. Mechanisms of Nonhomologous Repair of Damaged DNA
    Sang Eun Lee; Fiscal Year: 2005
    ..Furthermore, since DSB repair by NHEJ is remarkably conserved from yeast to humans, these studies will help to dissect the similar pathways in humans. ..
  59. Gonococcal Pilus Structure and Function
    H Seifert; Fiscal Year: 2008
    ..These studies will provide new findings and insights into the structure and functions of the gonococcal pilus. ..
  60. VIRUS CHROMOSOME STRUCTURE: ROLE IN DEVELOPMENT
    Michael Feiss; Fiscal Year: 2005
    ..We will also look at the ability of terminase to move DNA, and to pursue a structural analysis of functional domains of terminase. ..
  61. TARGETING ORIGINS OF REPLICATION WITH CANCER DRUGS
    WILLIAM BURHANS; Fiscal Year: 2004
    ..abstract_text> ..
  62. Endonuclease dificiency in breast cancer progression
    Alexei Basnakian; Fiscal Year: 2006
    ..The next specific aim will be focused on functional studies to determine the role of EndoG in dedifferentiation and invasiveness of breast cancer cells in vitro (Specific Aim 2). ..