replication origin

Summary

Summary: A unique DNA sequence of a replicon at which DNA REPLICATION is initiated and proceeds bidirectionally or unidirectionally. It contains the sites where the first separation of the complementary strands occurs, a primer RNA is synthesized, and the switch from primer RNA to DNA synthesis takes place. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)

Top Publications

  1. ncbi Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells
    Emily E Arias
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Genes Dev 21:497-518. 2007
  2. pmc Conservation of replication timing reveals global and local regulation of replication origin activity
    Carolin A Müller
    Centre for Genetics and Genomics, The University of Nottingham, Medical School, Queen s Medical Centre, Nottingham NG7 2UH, United Kingdom
    Genome Res 22:1953-62. 2012
  3. ncbi Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs
    Emilie Besnard
    Laboratory of Plasticity of the Genome and Aging, Functional Genomics Institute, Montpellier, France
    Nat Struct Mol Biol 19:837-44. 2012
  4. ncbi Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site
    Anne Letessier
    Institut Curie, Centre de Recherche, 26 Rue d Ulm, 75248 Paris, France
    Nature 470:120-3. 2011
  5. pmc OriDB, the DNA replication origin database updated and extended
    Cheuk C Siow
    Centre for Genetics and Genomics, The University of Nottingham, Queen s Medical Centre, Nottingham NG7 2UH, UK
    Nucleic Acids Res 40:D682-6. 2012
  6. pmc Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae
    Simon R V Knott
    Molecular and Computational Biology Program, University of Southern California, Los Angeles, CA 90089, USA
    Cell 148:99-111. 2012
  7. pmc Functional centromeres determine the activation time of pericentric origins of DNA replication in Saccharomyces cerevisiae
    Thomas J Pohl
    Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, United States of America
    PLoS Genet 8:e1002677. 2012
  8. ncbi Eukaryotic DNA replication origins: many choices for appropriate answers
    Marcel Mechali
    Institute of Human Genetics, CNRS, Montpellier, France
    Nat Rev Mol Cell Biol 11:728-38. 2010
  9. ncbi Eukaryotic chromosome DNA replication: where, when, and how?
    Hisao Masai
    Genome Dynamics Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156 8506, Japan
    Annu Rev Biochem 79:89-130. 2010
  10. ncbi Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing
    Seiji Tanaka
    Division of Microbial Genetics, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411 8540, Japan
    Curr Biol 21:2055-63. 2011

Detail Information

Publications321 found, 100 shown here

  1. ncbi Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells
    Emily E Arias
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Genes Dev 21:497-518. 2007
    ....
  2. pmc Conservation of replication timing reveals global and local regulation of replication origin activity
    Carolin A Müller
    Centre for Genetics and Genomics, The University of Nottingham, Medical School, Queen s Medical Centre, Nottingham NG7 2UH, United Kingdom
    Genome Res 22:1953-62. 2012
    ..To gain insight as to the mechanisms by which origin activation time is regulated we generated replication profiles for a S. cerevisiae/S. bayanus hybrid strain and find that there are both local and global regulators of origin function...
  3. ncbi Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs
    Emilie Besnard
    Laboratory of Plasticity of the Genome and Aging, Functional Genomics Institute, Montpellier, France
    Nat Struct Mol Biol 19:837-44. 2012
    ..Finally, we discovered a cell type-specific reprogrammable signature of cell identity that was revealed by specific efficiencies of conserved origin positions and not by the selection of cell type-specific subsets of origins...
  4. ncbi Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site
    Anne Letessier
    Institut Curie, Centre de Recherche, 26 Rue d Ulm, 75248 Paris, France
    Nature 470:120-3. 2011
    ..Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates...
  5. pmc OriDB, the DNA replication origin database updated and extended
    Cheuk C Siow
    Centre for Genetics and Genomics, The University of Nottingham, Queen s Medical Centre, Nottingham NG7 2UH, UK
    Nucleic Acids Res 40:D682-6. 2012
    ..oridb.org/) is a database containing collated genome-wide mapping studies of confirmed and predicted replication origin sites. The original database collated and curated Saccharomyces cerevisiae origin mapping studies...
  6. pmc Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae
    Simon R V Knott
    Molecular and Computational Biology Program, University of Southern California, Los Angeles, CA 90089, USA
    Cell 148:99-111. 2012
    ..chromosomes is organized temporally and spatially within the nucleus through epigenetic regulation of replication origin function...
  7. pmc Functional centromeres determine the activation time of pericentric origins of DNA replication in Saccharomyces cerevisiae
    Thomas J Pohl
    Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, United States of America
    PLoS Genet 8:e1002677. 2012
    ..Our results constitute a direct link between establishment of the kinetochore and the replication initiation machinery, and suggest that the proposed higher-order structure of the pericentric chromatin influences replication initiation...
  8. ncbi Eukaryotic DNA replication origins: many choices for appropriate answers
    Marcel Mechali
    Institute of Human Genetics, CNRS, Montpellier, France
    Nat Rev Mol Cell Biol 11:728-38. 2010
    ..This suggests that during evolution, the use of replication origins became more controlled by epigenetic mechanisms affecting chromosome dynamics and expression than by DNA synthesis per se...
  9. ncbi Eukaryotic chromosome DNA replication: where, when, and how?
    Hisao Masai
    Genome Dynamics Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156 8506, Japan
    Annu Rev Biochem 79:89-130. 2010
    ..We review here various regulatory mechanisms that control the replication program in eukaryotes and discuss future directions in this dynamic field...
  10. ncbi Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing
    Seiji Tanaka
    Division of Microbial Genetics, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411 8540, Japan
    Curr Biol 21:2055-63. 2011
    ..However, the molecular basis for such temporal regulation is poorly understood...
  11. pmc Chk1 regulates the density of active replication origins during the vertebrate S phase
    Apolinar Maya-Mendoza
    Faculty of Life Sciences, University of Manchester, MIB, Manchester, UK
    EMBO J 26:2719-31. 2007
    ..The same phenotype is induced in wild-type avian cells when Chk1 or ATM/ATR is inhibited. These observations show that Chk1 regulates replication origin activation and contributes to S-phase progression in somatic vertebrate cells.
  12. pmc Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features
    Christelle Cayrou
    Institute of Human Genetics, CNRS, Montpellier, France
    Genome Res 21:1438-49. 2011
    ..This organization provides both site specificity and Ori firing flexibility in each replicon, allowing possible adaptation to environmental cues and cell fates...
  13. pmc Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast
    Davide Mantiero
    Department of Zoology, Wellcome Trust Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Cambridge, UK
    EMBO J 30:4805-14. 2011
    ....
  14. ncbi Recruitment of condensin to replication origin regions by ParB/SpoOJ promotes chromosome segregation in B. subtilis
    Stephan Gruber
    Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
    Cell 137:685-96. 2009
    ..Our results demonstrate a direct functional interaction between two widely conserved systems involved in chromosome replication and segregation...
  15. pmc How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells?
    Karim Labib
    Cancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, United Kingdom
    Genes Dev 24:1208-19. 2010
    ..A series of recent studies has shed new light on the targets of Cdc7 and CDK, indicating that chromosome replication probably initiates by a fundamentally similar mechanism in all eukaryotes...
  16. pmc Replication initiation at the Escherichia coli chromosomal origin
    Jon M Kaguni
    Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 1319, USA
    Curr Opin Chem Biol 15:606-13. 2011
    ....
  17. pmc Replication fork stalling at natural impediments
    Ekaterina V Mirkin
    Department of Biology, Tufts University, Medford, MA 02155, USA
    Microbiol Mol Biol Rev 71:13-35. 2007
    ..This review describes the mechanisms and consequences of replication stalling at various natural impediments, with an emphasis on the role of replication stalling in genomic instability...
  18. pmc Maintaining replication origins in the face of genomic change
    Sara C Di Rienzi
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    Genome Res 22:1940-52. 2012
    ..We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved...
  19. pmc New insights into replication origin characteristics in metazoans
    Christelle Cayrou
    Institute of Human Genetics, CNRS, Montpellier, France
    Cell Cycle 11:658-67. 2012
    ..Finally, OGREs predict G-quadruplex structures at Oris that might be structural elements controlling the choice or activation of replication origins...
  20. pmc Quality control in the initiation of eukaryotic DNA replication
    John F X Diffley
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
    Philos Trans R Soc Lond B Biol Sci 366:3545-53. 2011
    ....
  21. ncbi Inhibition of eukaryotic DNA replication by geminin binding to Cdt1
    J A Wohlschlegel
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Science 290:2309-12. 2000
    ..In the normal cell cycle, Cdt1 is present only in G1 and S, whereas geminin is present in S and G2 phases of the cell cycle. Together, these results suggest that geminin inhibits inappropriate origin firing by targeting Cdt1...
  22. ncbi DNA replication initiation: mechanisms and regulation in bacteria
    Melissa L Mott
    Department of Molecular and Cell Biology, Quantitative Biology Institute, University of California, Berkeley, 237 Hildebrand Hall 3220, California 94720 3220, USA
    Nat Rev Microbiol 5:343-54. 2007
    ..This Review presents an overview of both the mechanism and regulation of bacterial DNA replication initiation, with emphasis on the features that are similar in eukaryotic and archaeal systems...
  23. pmc Conserved nucleosome positioning defines replication origins
    Matthew L Eaton
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Genes Dev 24:748-53. 2010
    The origin recognition complex (ORC) specifies replication origin location...
  24. ncbi Spatial and temporal organization of replicating Escherichia coli chromosomes
    Ivy F Lau
    Division of Molecular Genetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Mol Microbiol 49:731-43. 2003
    The positions of DNA regions close to the chromosome replication origin and terminus in growing cells of Escherichia coli have been visualized simultaneously, using new widely applicable reagents...
  25. pmc Genome-wide studies highlight indirect links between human replication origins and gene regulation
    Jean Charles Cadoret
    Institut Jacques Monod, Centre National de la Recherche Scientifique, University Paris 7, 75251 Paris cedex 5, France
    Proc Natl Acad Sci U S A 105:15837-42. 2008
    ..Replication timing analyses coupled with our origin mapping suggest that a relatively strict origin-timing program regulates the replication of the human genome...
  26. pmc Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation
    Philip Zegerman
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 467:474-8. 2010
    ..Our results explain how checkpoints regulate origin firing and demonstrate that the slowing of S phase by the 'intra-S checkpoint' is primarily due to the inhibition of origin firing...
  27. pmc Division of labor at the eukaryotic replication fork
    Stephanie A Nick McElhinny
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    Mol Cell 30:137-44. 2008
    ..strand-specific mutation rates strongly depend on the orientation of a reporter gene relative to an adjacent replication origin, in a manner implying that >90% of Pol delta replication is performed using the lagging strand template...
  28. ncbi Structural basis for ATP-dependent DnaA assembly and replication-origin remodeling
    Jan P Erzberger
    Division of Biochemistry and Molecular Biology, Molecular and Cell Biology Department, 327B Hildebrand Hall 3206, University of California, Berkeley, California 94720, USA
    Nat Struct Mol Biol 13:676-83. 2006
    ..Eukaryotic and archaeal initiators also have the structural elements that promote open-helix formation, indicating that a spiral, open-ring AAA+ assembly forms the core element of initiators in all domains of life...
  29. pmc Mathematical modelling of whole chromosome replication
    Alessandro P S de Moura
    Department of Physics, University of Aberdeen, Aberdeen AB24 3UE and School of Biology, University of Nottingham, Nottingham NG7 2UH, UK
    Nucleic Acids Res 38:5623-33. 2010
    ..In summary, we demonstrate that a stochastic model can recapitulate experimental observations, including those that might be interpreted as deterministic such as ordered origin activation times...
  30. pmc Modeling genome-wide replication kinetics reveals a mechanism for regulation of replication timing
    Scott Cheng Hsin Yang
    Department of Physics, Simon Fraser University, Burnaby, British Columbia, Canada
    Mol Syst Biol 6:404. 2010
    ..This model is the first to suggest a detailed, testable, biochemically plausible mechanism for the regulation of replication timing in eukaryotes...
  31. pmc DNA stretching by bacterial initiators promotes replication origin opening
    Karl E Duderstadt
    Biophysics Graduate Group, University of California, Berkeley, Berkeley, California 94720, USA
    Nature 478:209-13. 2011
    ..Comparative studies reveal notable commonalities between the approach used by DnaA to engage DNA substrates and other, nucleic-acid-dependent, AAA+ systems...
  32. ncbi The histone H4 Lys 20 methyltransferase PR-Set7 regulates replication origins in mammalian cells
    Mathieu Tardat
    Institut de Génétique Moléculaire de Montpellier IGMM, UMR 5535 CNRS, Montpellier, France
    Nat Cell Biol 12:1086-93. 2010
    ..These results elucidate a critical role for PR-Set7 and H4K20me1 in the chromatin events that regulate replication origins...
  33. pmc Epigenetically-inherited centromere and neocentromere DNA replicates earliest in S-phase
    Amnon Koren
    Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, USA
    PLoS Genet 6:e1001068. 2010
    ..albicans genome, we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome...
  34. pmc Independent positioning and action of Escherichia coli replisomes in live cells
    Rodrigo Reyes-Lamothe
    Department of Biochemistry, University of Oxford, Oxford OX1 3 QU, UK
    Cell 133:90-102. 2008
    ..We conclude that independent replication forks follow the path of the compacted chromosomal DNA, with no structure other than DNA anchoring the replisome to any particular cellular region...
  35. pmc Genome-wide identification and characterization of replication origins by deep sequencing
    Jia Xu
    Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Genome Biol 13:R27. 2012
    ..DNA replication initiates at distinct origins in eukaryotic genomes, but the genomic features that define these sites are not well understood...
  36. pmc Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication
    Arkaitz Ibarra
    DNA replication Group, Molecular Oncology Programme, Spanish National Cancer Research Centre CNIO, Melchor Fernandez Almagro, 3 E 28029 Madrid, Spain
    Proc Natl Acad Sci U S A 105:8956-61. 2008
    ..Our data show that the chromatin-bound "excess" Mcm2-7 complexes play an important role in maintaining genomic integrity under conditions of replicative stress...
  37. ncbi ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome
    C Liang
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 81:667-76. 1995
    ..We suggest that ORC and Cdc6p form a prereplication complex at individual replicators and therefore cooperate to determine the frequency of initiation of DNA replication in the genome...
  38. pmc The DNA damage response pathway contributes to the stability of chromosome III derivatives lacking efficient replicators
    James F Theis
    Department of Microbiology and Molecular Genetics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America
    PLoS Genet 6:e1001227. 2010
    ..Thus, components of the DNA damage response pathway contribute to genome stability, not simply by detecting and responding to DNA template damage, but also by facilitating replication of large inter-origin gaps...
  39. pmc Caulobacter requires a dedicated mechanism to initiate chromosome segregation
    Esteban Toro
    Department of Developmental Biology, Stanford University School of Medicine, Beckman Center, B300, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 105:15435-40. 2008
    ..Also, a mutation in the ATPase domain of ParA halts segregation without affecting replication initiation. Chromosome segregation in Caulobacter cannot occur unless a dedicated parS guiding mechanism initiates movement...
  40. ncbi ATPase-dependent quality control of DNA replication origin licensing
    Jordi Frigola
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK
    Nature 495:339-43. 2013
    ..Our work provides new insights into how origins are licensed and reveals a novel ATPase-dependent mechanism contributing to precise once per cell cycle replication...
  41. pmc The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation
    Hui Yong Lian
    Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK
    Mol Biol Cell 22:1753-65. 2011
    ....
  42. pmc Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases
    Ryan C Heller
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Cell 146:80-91. 2011
    ..Our studies identify distinct roles for DDK and S-CDK during helicase activation and support a model in which the leading strand DNA polymerase is recruited prior to origin DNA unwinding and RNA primer synthesis...
  43. pmc Genome-wide mapping of Arabidopsis thaliana origins of DNA replication and their associated epigenetic marks
    Celina Costas
    Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Madrid, Spain
    Nat Struct Mol Biol 18:395-400. 2011
    ..Z, H3K4me2, H3K4me3 and H4K5ac, and depleted in H3K4me1 and H3K9me2. Our data help clarify the epigenetic specification of DNA replication origins in A. thaliana and have implications for other eukaryotes...
  44. pmc Nucleosomal organization of replication origins and meiotic recombination hotspots in fission yeast
    Elisa de Castro
    Instituto de Biología Funcional y Genómica, CSIC Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, Salamanca, Spain
    EMBO J 31:124-37. 2012
    ..The organization of ORIs and of DSBs regions in S. pombe reveals similarities and differences relative to Saccharomyces cerevisiae...
  45. pmc Molecular determinants of origin discrimination by Orc1 initiators in archaea
    Erin C Dueber
    Department of Molecular Biology, 374D Stanley Hall 3220, University of California at Berkeley, Berkeley, CA, 94707, USA
    Nucleic Acids Res 39:3621-31. 2011
    ..Our results show that both the WHD and ATPase region influence origin recognition by Orc1/Cdc6, and suggest that not only DNA sequence, but also local DNA structure help define archaeal initiator binding sites...
  46. ncbi Formation of an ATP-DnaA-specific initiation complex requires DnaA Arginine 285, a conserved motif in the AAA+ protein family
    Hironori Kawakami
    Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    J Biol Chem 280:27420-30. 2005
    ....
  47. pmc How dormant origins promote complete genome replication
    J Julian Blow
    Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee Dow Street, Dundee DD1 5EH, UK
    Trends Biochem Sci 36:405-14. 2011
    ..We review the function of dormant origins, the molecular mechanism of their regulation and their physiological implications...
  48. pmc Rif1 is a global regulator of timing of replication origin firing in fission yeast
    Motoshi Hayano
    Genome Dynamics, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo, Japan
    Genes Dev 26:137-50. 2012
    ..Our data demonstrate that Rif1 is a critical determinant of the origin activation program on the fission yeast chromosomes...
  49. pmc Damage-induced phosphorylation of Sld3 is important to block late origin firing
    Jaime Lopez-Mosqueda
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158 9001, USA
    Nature 467:479-83. 2010
    ..These data indicate that the intra-S-phase checkpoint functions to block late origin firing in adverse conditions to prevent genomic instability and maximize cell survival...
  50. ncbi Cell cycle-dependent polar localization of chromosome partitioning proteins in Caulobacter crescentus
    D A Mohl
    Department of Chemistry and Biochemistry and Molecular Biology Institute, University of California, Los Angeles 90095 1569, USA
    Cell 88:675-84. 1997
    ..These results suggest that ParA and ParB are involved in partitioning newly replicated chromosomes to the poles of the predivisional cell and may function as components of a bacterial mitotic apparatus...
  51. pmc Dancing around the divisome: asymmetric chromosome segregation in Escherichia coli
    Xindan Wang
    Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom
    Genes Dev 19:2367-77. 2005
    ..As ter duplicates at mid-cell, sister nucleoid separation appears complete. After initiation of invagination, the FtsZ ring disassembles, leaving FtsK to complete chromosome segregation and cytokinesis...
  52. pmc Extrachromosomal element capture and the evolution of multiple replication origins in archaeal chromosomes
    Nicholas P Robinson
    Medical Research Council Cancer Cell Unit, Hutchison Medical Research Council Research Center, Hills Road, Cambridge CB2 0XZ, United Kingdom
    Proc Natl Acad Sci U S A 104:5806-11. 2007
    ..Recently, the multiple replication origin paradigm has also been demonstrated within the archaeal domain of life, with the discovery that the ..
  53. pmc Three replication origins in Sulfolobus species: synchronous initiation of chromosome replication and asynchronous termination
    Magnus Lundgren
    Department of Molecular Evolution, Evolutionary Biology Center, Uppsala University, Norbyvagen 18C, SE 752 36 Uppsala, Sweden
    Proc Natl Acad Sci U S A 101:7046-51. 2004
    ..In S. acidocaldarius, a region containing short regularly spaced repeats was found to hybridize aberrantly, as compared to the rest of the chromosome, raising the possibility of a centromere-like function...
  54. ncbi Replication dynamics of the yeast genome
    M K Raghuraman
    Department of Genetics, Department of Mathematics, University of Washington, Seattle, WA 98195, USA
    Science 294:115-21. 2001
    ..The two ends of each of the 16 chromosomes are highly correlated in their times of replication. This microarray approach is readily applicable to other organisms, including humans...
  55. ncbi Progressive segregation of the Escherichia coli chromosome
    Henrik J Nielsen
    BioCentrum DTU, Technical University of Denmark, DK 2800 Kgs Lyngby, Denmark
    Mol Microbiol 61:383-93. 2006
    ..Segregation appears to leave one copy of each locus in place, and rapidly transport the other to the other side of the cell centre...
  56. ncbi Distinct segregation dynamics of the two Vibrio cholerae chromosomes
    Michael A Fogel
    Program in Genetics, Tufts University School of Medicine, Boston, MA, USA
    Mol Microbiol 55:125-36. 2005
    ..The differences in localization and timing of segregation of oriCIvc and oriCIIvc suggest that distinct mechanisms govern the segregation of the two V. cholerae chromosomes...
  57. pmc Identification of short 'eukaryotic' Okazaki fragments synthesized from a prokaryotic replication origin
    Fujihiko Matsunaga
    Universite Paris Sud, Orsay, France
    EMBO Rep 4:154-8. 2003
    ..Short Okazaki fragments and a high replication speed imply a very efficient turnover of Okazaki fragments in Archaea. Archaea therefore have a unique replication system showing mechanistic similarities to both Bacteria and Eukarya...
  58. ncbi The N-terminus promotes oligomerization of the Escherichia coli initiator protein DnaA
    C Weigel
    Max Planck Institut fur Molekulare Genetik, Ihnestrasse 73, D 14195 Berlin Dahlem, Germany
    Mol Microbiol 34:53-66. 1999
    ..replication in Escherichia coli is governed by the interaction of the initiator protein DnaA with the replication origin oriC...
  59. pmc A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication
    Marcin Pacek
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA
    EMBO J 23:3667-76. 2004
    ..These results provide new support for the model that MCM2-7 is the replicative DNA helicase, and they indicate that Cdc45 functions as a helicase co-factor...
  60. ncbi Epigenomic replication: linking epigenetics to DNA replication
    Adrian J McNairn
    Department of Biochemistry and Molecular Biology, S U N Y Syracuse, NY 13210, USA
    Bioessays 25:647-56. 2003
    ..Since transcriptionally active and inactive chromosome domains generally replicate at different times during S-phase, this spatiotemporal regulation of chromatin assembly proteins may be an integral part of epigenetic inheritance...
  61. pmc Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin
    S Tada
    CRC Chromosome Replication Research Group, Wellcome Trust Biocentre, Dow Street University of Dundee, Dundee DD1 5EH, UK
    Nat Cell Biol 3:107-13. 2001
    ..These experiments suggest that geminin-mediated inhibition of RLF-B/Cdt1 is essential for repressing origin assembly late in the cell cycle of higher eukaryotes...
  62. ncbi Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex
    R D Klemm
    Massachusetts Institute of Technology, Department of Biology, Cambridge 02139, USA
    Cell 88:493-502. 1997
    ..These data demonstrate that occupancy of the Orc1p ATP-binding site has a profound effect on ORC function and that ATP hydrolysis by Orc1p has the potential to drive transitions between different functional states of ORC...
  63. pmc Primase directs the release of DnaC from DnaB
    Magdalena Makowska-Grzyska
    Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824 1319, USA
    Mol Cell 37:90-101. 2010
    ..The interaction of primase with DnaB and the release of DnaC mark discrete events in the transition from initiation to the elongation stage of DNA replication...
  64. ncbi Mcm10 plays a role in functioning of the eukaryotic replicative DNA helicase, Cdc45-Mcm-GINS
    George Watase
    Center for Frontier Research, National Institute of Genetics, Research Organization of Information and Systems, Yata 1111, Mishima, Shizuoka 411 8540, Japan
    Curr Biol 22:343-9. 2012
    ..Thus, Mcm10 plays an essential role in functioning of the CMG replicative helicase independent of assembly of a stable CMG complex at origins...
  65. pmc Regulation of DnaA assembly and activity: taking directions from the genome
    Alan C Leonard
    Department of Biological Sciences, Florida Institute of Technology, Melbourne, Florida 32901, USA
    Annu Rev Microbiol 65:19-35. 2011
    ..bacteria must carefully regulate the activity of initiator protein DnaA and its interactions with the unique replication origin oriC...
  66. pmc Replication cycle-coordinated change of the adenine nucleotide-bound forms of DnaA protein in Escherichia coli
    K Kurokawa
    Department of Molecular Microbiology, Kyushu University Graduate School of Pharmaceutical Sciences, 3 1 1 Maidashi, Higashi ku, Fukuoka, 812 8582, Japan
    EMBO J 18:6642-52. 1999
    ..Regeneration of ATP-DnaA from ADP-DnaA was also observed. These results indicate that the nucleotide form shifts of DnaA are tightly linked with an epistatic cell cycle event and with the chromosomal replication system...
  67. pmc The fission yeast homologue of Orc4p binds to replication origin DNA via multiple AT-hooks
    R Y Chuang
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21210, USA
    Proc Natl Acad Sci U S A 96:2656-61. 1999
    ..The Orp4 protein (and its isolated N-terminal domain) binds to the Sc. pombe replication origin, ars1...
  68. pmc Pre-replication complex proteins assemble at regions of low nucleosome occupancy within the Chinese hamster dihydrofolate reductase initiation zone
    Yoav Lubelsky
    Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA
    Nucleic Acids Res 39:3141-55. 2011
    ....
  69. pmc Regulation of heterochromatic DNA replication by histone H3 lysine 27 methyltransferases
    Yannick Jacob
    Department of Biology, Indiana University, 915 East Third Street, Bloomington, Indiana 47405, USA
    Nature 466:987-91. 2010
    ..Mutation of ATXR5 and ATXR6 also causes upregulation of transposon expression and has pleiotropic effects on plant development. These results uncover a novel pathway that prevents over-replication of heterochromatin in Arabidopsis...
  70. ncbi The ParB protein of Streptomyces coelicolor A3(2) recognizes a cluster of parS sequences within the origin-proximal region of the linear chromosome
    Dagmara Jakimowicz
    John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK
    Mol Microbiol 45:1365-77. 2002
    ..multiple ParB molecules may assemble along the DNA from an initial ParB-parS complex, suggest that a large DNA segment around the replication origin may form a massive nucleoprotein complex as part of the replication-partitioning cycle.
  71. pmc Global effects of DNA replication and DNA replication origin activity on eukaryotic gene expression
    Larsson Omberg
    Department of Biomedical Engineering, University of Texas, Austin, TX 78712, USA
    Mol Syst Biol 5:312. 2009
    ..This confirms previous predictions from mathematical modeling of a global causal coordination between DNA replication origin activity and mRNA expression, and shows that mathematical modeling of DNA microarray data can be used to ..
  72. ncbi Escherichia coli DnaA protein. The N-terminal domain and loading of DnaB helicase at the E. coli chromosomal origin
    M D Sutton
    Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824 1319, USA
    J Biol Chem 273:34255-62. 1998
    ..Based on similarities in the replication process between prokaryotes and eukaryotes, these results suggest that a similar mechanism may load the eukaryotic replicative helicase...
  73. ncbi ORC proteins: marking the start
    Dale B Wigley
    Cancer Research UK Clare Hall Laboratories, The London Research Institute, Blanche Lane, South Mimms, Potters Bar, Herts, UK
    Curr Opin Struct Biol 19:72-8. 2009
    ..Crystal structures of archaeal replication origin binding proteins complexed with their DNA targets revealed details of how they interact with origins and ..
  74. pmc Transcription initiation activity sets replication origin efficiency in mammalian cells
    Joana Sequeira-Mendes
    Edificio Departamental, Instituto de Microbiologia Bioquimica, CSIC Universidad de Salamanca, Salamanca, Spain
    PLoS Genet 5:e1000446. 2009
    ..This association implies that transcription initiation early in development sets the probability of ORI activation, unveiling a new hallmark in ORI efficiency regulation in mammalian cells...
  75. ncbi The DNA replication checkpoint response stabilizes stalled replication forks
    M Lopes
    Istituto F.I.R.C. di Oncologia Molecolare, Via Serio 21, 20141, Milano, Italy
    Nature 412:557-61. 2001
    ..Further, Rad53 is required to properly maintain stable replication forks during the block. We propose that Rad53 prevents collapse of the fork when replication pauses...
  76. pmc Replicon dynamics, dormant origin firing, and terminal fork integrity after double-strand break formation
    Ylli Doksani
    FIRC Institute of Molecular Oncology Foundation IFOM IEO Campus and DSBB Università degli Studi di Milano, Via Adamello 16, 20139 Milan, Italy
    Cell 137:247-58. 2009
    ..Our findings have implications for those genome instability syndromes that accumulate DNA breaks during S phase and for forks encountering eroding telomeres...
  77. ncbi Cell cycle-dependent establishment of a late replication program
    M K Raghuraman
    Department of Genetics, University of Washington, Box 35 7360, Seattle, WA 98195 7360, USA
    Science 276:806-9. 1997
    ..Once set, the signal can persist through the next S phase in the absence of the telomere. Establishment of the temporal program and of initiation competence of origins may be coincident events...
  78. pmc Replication-dependent instability at (CTG) x (CAG) repeat hairpins in human cells
    Guoqi Liu
    Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA
    Nat Chem Biol 6:652-9. 2010
    ..lines in which (CTG) x (CAG) repeats are replicated from an ectopic copy of the Myc (also known as c-myc) replication origin. In this system, the tendency of chromosomal (CTG) x (CAG) tracts to expand or contract was affected by ..
  79. pmc Evaluating genome-scale approaches to eukaryotic DNA replication
    David M Gilbert
    Department of Biological Science, Florida State University, Tallahassee, 32306, USA
    Nat Rev Genet 11:673-84. 2010
    ....
  80. pmc Dynamic organization of chromosomal DNA in Escherichia coli
    H Niki
    Unit Process and Combined Circuit, PRESTO, Japan Science and Technology Corporation JST, Kumamoto, 862 0976, Japan
    Genes Dev 14:212-23. 2000
    ..These studies thus suggest that the E. coli chromosome is organized to form a compacted ring structure with the Ori and Ter domains; these domains participate in the cell cycle-dependent localization of the chromosome...
  81. ncbi Branch migrating sister chromatid junctions form at replication origins through Rad51/Rad52-independent mechanisms
    Massimo Lopes
    Istituto F I R C di Oncologia Molecolare, Via Adamello 16, Milano 20141, Italy
    Mol Cell 12:1499-510. 2003
    ....
  82. pmc Genetic and physical mapping of DNA replication origins in Haloferax volcanii
    Cedric Norais
    Institut de Genetique et Microbiologie, Universite Paris Sud, Orsay, France
    PLoS Genet 3:e77. 2007
    ..Our observations also suggest that H. volcanii is an ideal organism for studying how replication of four replicons is regulated in the context of the archaeal cell cycle...
  83. ncbi Visualization of DNA replication on individual Epstein-Barr virus episomes
    P Norio
    Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Science 294:2361-4. 2001
    ..We conclude that initiation zones and pausing sites are major organizers of the duplication program, but initiation, fork progression, and termination of replication can vary in each molecule...
  84. pmc GEMC1 is a TopBP1-interacting protein required for chromosomal DNA replication
    Alessia Balestrini
    Genome Stability, London Research Institute, Hertfordshire, UK
    Nat Cell Biol 12:484-91. 2010
    ..These data suggest that GEMC1 promotes initiation of chromosomal DNA replication in multicellular organisms by mediating TopBP1- and Cdk2-dependent recruitment of Cdc45 onto replication origins...
  85. pmc DNA adenine methylation is required to replicate both Vibrio cholerae chromosomes once per cell cycle
    Gaëlle Demarre
    Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
    PLoS Genet 6:e1000939. 2010
    ..cholerae. The structure of oriII suggests that it originated from a plasmid, but unlike plasmids, oriII makes use of methylation for once-per-cell-cycle replication, the norm for chromosomal but not plasmid replication...
  86. ncbi A common mechanism for the ATP-DnaA-dependent formation of open complexes at the replication origin
    Shogo Ozaki
    Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
    J Biol Chem 283:8351-62. 2008
    ..Escherichia coli DnaA protein forms a homomultimeric complex with the replication origin (oriC). ATP-DnaA multimers unwind the duplex within the oriC unwinding element (DUE)...
  87. pmc Treslin collaborates with TopBP1 in triggering the initiation of DNA replication
    Akiko Kumagai
    Division of Biology 147 75, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 140:349-59. 2010
    ..Taken together, these results indicate that Treslin and TopBP1 collaborate in the Cdk2-mediated loading of Cdc45 onto replication origins. Thus, Treslin regulates a pivotal step in the initiation of DNA replication in vertebrates...
  88. pmc Diversity of eukaryotic DNA replication origins revealed by genome-wide analysis of chromatin structure
    Nicolas M Berbenetz
    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    PLoS Genet 6:e1001092. 2010
    ..occludes nucleosomes to permit binding of the origin recognition complex, which then (likely in concert with nucleosome modifiers and remodelers) positions nucleosomes adjacent to the origin to promote replication origin function.
  89. ncbi Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin
    S K Dhar
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Cell 106:287-96. 2001
    ..Geminin, an inhibitor of the mammalian replication initiation complex, inhibits replication from oriP. Therefore, ORC and the human replication initiation apparatus is required for replication from a viral origin of replication...
  90. pmc Structural basis of replication origin recognition by the DnaA protein
    Norie Fujikawa
    RIKEN Genomic Sciences Center, 1 7 22 Suehiro cho, Tsurumi, Yokohama 230 0045, Japan
    Nucleic Acids Res 31:2077-86. 2003
    Escherichia coli DnaA binds to 9 bp sequences (DnaA boxes) in the replication origin, oriC, to form a complex initiating chromosomal DNA replication...
  91. pmc Hda, a novel DnaA-related protein, regulates the replication cycle in Escherichia coli
    J Kato
    Department of Biology, Tokyo Metropolitan University, Minamiohsawa, Hachioji, Tokyo 192 0397, Japan
    EMBO J 20:4253-62. 2001
    ..We propose that the once-per-cell-cycle rule of replication depends on the timely interaction of AAA(+) proteins that comprise the apparatus regulating the activity of the initiator of replication...
  92. ncbi XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis
    D Maiorano
    Institute of Human Genetics, CNRS, Genome Dynamics and Development, Montpellier, France
    Nature 404:622-5. 2000
    ..These findings indicate that XCDT1 is an essential component of the system that regulates origins firing during S phase...
  93. ncbi The 'ORC cycle': a novel pathway for regulating eukaryotic DNA replication
    Melvin L DePamphilis
    National Institute of Child Health and Human Development, Building 6 416, 9000 Rockville Pike, National Institutes of Health, Bethesda, MD 20892 2753, USA
    Gene 310:1-15. 2003
    ....
  94. ncbi DnaA, ORC, and Cdc6: similarity beyond the domains of life and diversity
    Hironori Kawakami
    Cold Spring Harbor Laboratory, 1 Bungtown Rd, Cold Spring Harbor, NY 11724, USA
    Biochem Cell Biol 88:49-62. 2010
    To initiate chromosomal DNA replication, specific proteins bind to the replication origin region and form multimeric and dynamic complexes...
  95. pmc The complete genome sequence of the murine respiratory pathogen Mycoplasma pulmonis
    I Chambaud
    , , 71 Avenue Edouard Bourleaux, BP 81, 33883 Villenave d'Ornon Cedex, France
    Nucleic Acids Res 29:2145-53. 2001
    ..The genome contains a single set of rRNA genes and only 29 tRNAs genes. The replication origin oriC was localized by sequence analysis and by using the G + C skew method...
  96. pmc Global organization of replication time zones of the mouse genome
    Shlomit Farkash-Amar
    Department of Molecular Biology, Hebrew University Medical School Jerusalem 91120, Israel
    Genome Res 18:1562-70. 2008
    ..These findings, along with the strong conservation found between replication timing in human and mouse genomes, emphasize the importance of replication timing in transcription regulation...
  97. ncbi Restoration of growth to acidic phospholipid-deficient cells by DnaA(L366K) is independent of its capacity for nucleotide binding and exchange and requires DnaA
    Zhenya Li
    Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, 3900 Reservoir Rd NW, Washington, DC 20007, USA
    J Biol Chem 280:9796-801. 2005
    ....
  98. pmc Effects of Friedreich's ataxia GAA repeats on DNA replication in mammalian cells
    Gurangad S Chandok
    Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16802, USA
    Nucleic Acids Res 40:3964-74. 2012
    ..the transfected DNA replication occurs in the lack of the mature chromatin, does not depend on the episomal replication origin and initiates at multiple single-stranded regions of plasmid DNA...
  99. pmc Bacterial origin recognition complexes direct assembly of higher-order DnaA oligomeric structures
    Diana T Miller
    Department of Biological Sciences, Florida Institute of Technology, 150 West University Boulevard, Melbourne, FL 32901, USA
    Proc Natl Acad Sci U S A 106:18479-84. 2009
    ..We propose that in bacteria, DnaA oligomers of limited length and stability emerge from single high-affinity sites and extend toward weak sites to facilitate their loading as a key stage of prokaryotic pre-RC assembly...
  100. pmc Soj/ParA stalls DNA replication by inhibiting helix formation of the initiator protein DnaA
    Graham Scholefield
    Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK
    EMBO J 31:1542-55. 2012
    ..oligomer built upon interactions between neighbouring AAA+ domains, that in vitro stretches DNA to promote replication origin opening...
  101. pmc A distinct first replication cycle of DNA introduced in mammalian cells
    Gurangad S Chandok
    Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16801, USA
    Nucleic Acids Res 39:2103-15. 2011
    ..This work demonstrates, for the first time, differences in the replication progression during the first and subsequent replication cycles in mammalian cells...

Research Grants62

  1. Integrating stress MAP kinase signaling with DNA replication origin licensing
    Jeanette Gowen Cook; Fiscal Year: 2013
    ....
  2. Analysis of the Human c-myc Gene Replication Origin
    Michael Leffak; Fiscal Year: 2012
    ..Our laboratory identified the replication origin 5'to the human c-myc oncogene, and we have shown that the structure, protein binding and function of ..
  3. The molecular basis of RECQ4-associated genetic disorders and cancer predispositi
    Yilun Liu; Fiscal Year: 2013
    ..Importantly, complex formation and the association of RECQ4 with the replication origin are cell cycle regulated...
  4. Papillomavirus E2 Functions: Cellular Regulation and Effectors
    Peter M Howley; Fiscal Year: 2013
    ..replication as an auxiliary DNA replication factor that helps recruit the viral E1 helicase to the viral DNA replication origin. In addition, E2 is essential for genome maintenance in infected cells and, for some papillomaviruses, E2 ..
  5. REGULATORY INTERACTIONS BETWEEN TUMOR VIRUSES AND CELLS
    Michael R Botchan; Fiscal Year: 2013
    ..by complexes such as the MMB/Dream with the recruitment of proteins required for the basic function of a replication origin is another goal of this project...
  6. KSHV Lytic DNA Replication and its Control Mechanism
    Subhash C Verma; Fiscal Year: 2013
    ..data, this hypothesis will be tested by pursuing three specific aims: 1) Identification of the functional replication origin and the mechanism of lytic DNA replication using SMARD, 2) Determining the control mechanism of oriLyt-..
  7. Linking DNA Replication Origin Licensing with Cell Cycle Progression
    Kate E Coleman; Fiscal Year: 2013
    ..Ultimately, we anticipate that the long-term analysis of newly identified origin licensing regulators from these studies will guide the development of novel therapeutics for many human cancers. ..
  8. Replication Licensing in Genome Stability, Cancer and Aging
    Steven C Pruitt; Fiscal Year: 2013
    ..machinery, Mcm2, which is proving to be extremely valuable in understanding the consequences of deficient replication origin licensing...
  9. REGULATION OF TRYPANOSOME DNA REPLICATION
    Dan S Ray; Fiscal Year: 2013
    ..UMSBP and P38 have been implicated in playing a direct role in initiation of DNA synthesis at the minicircle replication origin. Both proteins will be expressed as recombinant proteins and will be available as components of the initial ..
  10. REGULATION OF TRYPANOSOME DNA REPLICATION
    DAN RAY; Fiscal Year: 2009
    ..the specific mitochondrial DNA polymerase that might function together with LIG ka? in gap repair and will examine the ability of the ligase-polymerase complex to repair a model minicircle gap at the replication origin.
  11. Understanding the mechanism of KSHV latent DNA replication
    Subhash C Verma; Fiscal Year: 2011
    ..to understand the mechanism of KSHV latent DNA replication more specifically mapping of the LANA independent replication origin, sequence requirement and protein dynamics at replication initiation sites to specifically block KSHV ..
  12. Molecular Mechanisms of Impaired DAN Damage Response in Leukemia Pathogenesis
    James J D Hsieh; Fiscal Year: 2012
    ..ATR phosphorylates and thus stabilizes MLL, (3) upon checkpoint activation MLL accumulates at the late replication origin, methylates histone H3K4, and thus delays DNA replication, (4) MLL deficient cells exhibit defects in the S-..
  13. Molecular Mechanisms of Impaired DAN Damage Response in Leukemia Pathogenesis
    James J D Hsieh; Fiscal Year: 2013
    ..ATR phosphorylates and thus stabilizes MLL, (3) upon checkpoint activation MLL accumulates at the late replication origin, methylates histone H3K4, and thus delays DNA replication, (4) MLL deficient cells exhibit defects in the S-..
  14. Investigation of DnaB helicase loading for initiating DNA replication
    VALERIE LYNN O'SHEA; Fiscal Year: 2011
    ..hexameric ring of DnaB must first be opened and deposited onto the single-stranded DNA regions of a melted replication origin, a process that depends on the initiator protein, DnaA, and the DnaB loading partner, DnaC...
  15. E1A Oncoprotein Induced Deregulation of Replication Origin Firing
    Bayar Thimmapaya; Fiscal Year: 2012
    ..These cells contain increased cellular DNA replication origin activity...
  16. Regulation of DNA replication by histone modifications
    Toshio Tsukiyama; Fiscal Year: 2013
    ..grant, we have developed an extremely efficient system to purify histones that are located near an active replication origin. Combined with ultra-sensitive mass spectrometry analyses, we identified previously unknown patterns of ..
  17. MiniPlasmid vector platform for non-viral gene therapy
    James Williams; Fiscal Year: 2013
    ..combine transient expression enhancers that improve transgene expression levels with a novel 270 base pair replication origin-antibiotic free selection cassette that we hypothesize will promote long duration gene expression after ..
  18. Okazaki Fragment Synthesis and Chromatin Assembly
    Iestyn Whitehouse; Fiscal Year: 2013
    ..In addition, we will determine the firing characteristics of each replication origin allowing us to tell when, how often, and for how long a particular origin is active...
  19. DNA REPLICATION INITIATION SITES IN MAMMALIAN CELLS
    Carl L Schildkraut; Fiscal Year: 2013
    ..our preliminary data, we expect these proposed studies will both greatly increase our understanding of telomere and TNR replication and allow us to establish new paradigms for the role replication origin selection in health and disease.
  20. The Structural Basis of Eukaryotic Replication Origin Licensing by Cryo-EM
    Huilin Li; Fiscal Year: 2010
    ..Yeast ORC constitutively binds to and marks the replication origin throughout the cell cycle...
  21. Control of Genome Stability by Replicative DNA Polymerases
    Youri I Pavlov; Fiscal Year: 2012
    ..In one approach we will study the distribution of mutation hotspots in the reporter placed near the replication origin in strains with inaccurate Pol a...
  22. Structure/Function Studies of DNA Replication Initiation
    James M Berger; Fiscal Year: 2013
    ..we will answer fundamental questions involving how initiation proteins collaborate to open a bubble in a replication origin and deposit ring-shaped helicases onto the DNA...
  23. REPLICATION AND AMPLIFICATION OF TETRAHYMENA RDNA
    Geoffrey Kapler; Fiscal Year: 2000
    ..Mechanisms that prevent reinitiation from a replication origin in a given S phase are not understood...
  24. STRUCTURE AND GENETIC CONTROL OF COLICINES
    Donald Helinski; Fiscal Year: 2005
    ..RK2 encodes a replication initiation protein (TrfA) and a replication origin that has as its main features 17 base pair repeats (iterons) that are bound by the TrfA protein, four DnaA ..
  25. Structural Basis of Large T Helicase Function in SV40 DNA Replication
    Xiaojiang S Chen; Fiscal Year: 2013
    ..e. marking the replication origin, recruiting helicase, melting origin, and activating helicase...
  26. MODULATION OF ORI-BETA REPLICATION ORIGIN BY FISH OIL
    Nawfal Istfan; Fiscal Year: 2004
    ..These effects are associated with a change in the activity at the replication origin (ori-beta) located within the dihydrofolate reductase (DHFR) gene in CHO cells...
  27. NUTRITION AND PROTEIN METABOLISM IN TUMOR AND HOST
    Nawfal Istfan; Fiscal Year: 2000
    ..in several proliferating cell lines and this effect is associated with a change in the location of a DNA replication origin; and (2) Levels of PDGF receptor mRNA are significantly increased in fibroblasts treated with fish oil. Dr...
  28. HERPES SIMPLEX VIRUS MULTIPLICATION
    Bernard Roizman; Fiscal Year: 1991
    ..defective genome concatemers were generated by replication of seed monomeric repeats containing a viral DNA replication origin and an a sequence, containing a cleavage/packaging signal...
  29. Regulation of DnaA and replication initiation in Bacillus subtilis
    RICHARD WEART; Fiscal Year: 2009
    ..initiation, which serves as a simplified model due to the presence of a single chromosome with a single replication origin, oriC, and a single replication initiation protein, DnaA...
  30. NUCLEOPROTEIN STRUCTURES AND GENOME DUPLICATION
    Marcin Filutowicz; Fiscal Year: 2002
    DESCRIPTION (adapted from investigator's abstract): Recognition of the replication origin by initiator protein is the central event regulating DNA replication in diverse biological systems...
  31. MOLECULAR BASIS OF CO1E1 REPLICATION CONTROL
    Barry Polisky; Fiscal Year: 1992
    ..of nascent primer RNA so that the primer is unable to form an RNA-DNA hybrid in the vicinity of the replication origin. A critical feature of the inhibition by RNA 1 is that it must interact with primer during a particular ..
  32. REPLICATION MECHANISM OF DRUG INDUCED GENE AMPLIFICATION
    Daniel Fernandes; Fiscal Year: 2000
    ..of DHFR sequences will be monitored as well as the accumulation of RNA-primed DNA at or downstream of the replication origin of the c-myc gene...
  33. BRASSICA CAMPESTRIS MITOCHONDRIAL DNA REPLICATION ORIGIN
    BRENT NIELSEN; Fiscal Year: 1993
    ..campestris, and for understanding mitochondrial DNA replication in other eukaryotic systems which have a more complex genome than in animal cells. ..
  34. REPLICATION AND POLYTENIZATION IN DROSOPHILA DEVELOPMENT
    Terry Orr Weaver; Fiscal Year: 1992
    ..In some tissues specific genomic regions are under or overreplicated as a result of an uncoupling of DNA replication origin usage from the cell cycle...
  35. DRUG RESISTANCE AND GENE AMPLIFICATION IN EUKARYOTES
    Geoffrey Wahl; Fiscal Year: 1992
    ..A replication origin present in one such element described previously in this lab will be isolated and analyzed in order to ..
  36. eukaryotic expression vectors resistant to transgene silencing
    James Williams; Fiscal Year: 2007
    ..Second, we hypothesize that one or more structured regions within the replication origin form unusual structures that recruits heterochromatin and accounts for the silencing...
  37. Tiling Path Microarray Re-amplifable Resource Drosophila
    Kevin White; Fiscal Year: 2006
    ..These arrays can be used for DNA-protein interaction mapping, comprehensive expression profiling, replication origin mapping, comparative genomic hybridization, physical mapping of deletions, and other applications...
  38. DNAA PROTEIN AND REPLICATION INITIATION IN MYCOBACTE
    Malini Rajagopalan; Fiscal Year: 1999
    ..Studies on replication initiation in other bacteria suggest that both DnaA, the initiator protein and replication origin sequences are structurally conserved...
  39. INITIATION OF DNA REPLICATION IN THE PHAGE T4 SYSTEM
    Kenneth Kreuzer; Fiscal Year: 2000
    ..replication focus on the role of a persistent RNA-DNA hybrid (R loop) that were recently detected at a t$ replication origin in the applicant's laboratory...
  40. REGULATION OF DNA REPLICATION AND CELL GROWTH
    Joel Huberman; Fiscal Year: 1992
    ..The other two projects will provide detailed information about aspects of replication origin structure and function...
  41. Role of Ddk Kinase in Regulation of DNA Replication
    Wei Jiang; Fiscal Year: 2006
    ..may be directly involved in regulating the initiation of DNA replication by phosphorylating chromatin/replication origin-associated proteins, such as MCM2, that orchestrate the initiation of DNA replication in mammalian cells...
  42. BACTERIOPHAGE LAMBDA DNA REPLICATION IN VITRO
    Roger McMacken; Fiscal Year: 2000
    ..P replication proteins promote the assembly of an ordered series of nucleoprotein structures at the lambda replication origin (ori- lambda) prior to priming and DNA chain elongation...
  43. A NOVEL FUNCTION OF THE SIMIAN VIRUS 40 GENOME
    Dana Carroll; Fiscal Year: 1980
    ..and defective genomes shows that, with one possible exception, they all have retained, in addition to the replication origin at map position 0.67, either a portion of the viral DNA near map position 0.16 or a host DNA substitution...
  44. STRUCTURE AND SYNTHESIS OF DNA
    PAUL ENGLUND; Fiscal Year: 1999
    ..The substrate will be a plasmid containing a minicircle replication origin, and proteins will be provided by a mitochondrial extract...
  45. Single Molecule Studies of Replication Origin in Metazoa
    Zhifeng Shao; Fiscal Year: 2007
    ..When such methods are combined with other established techniques, we will be able to further unravel various molecular determinants and the fundamental principles of genomic replication that should also have practical implications. ..
  46. MAMMALIAN DNA REPLICATION ORIGINS
    Joel Huberman; Fiscal Year: 1990
    The long-term goals of the proposed experiments are (i) to identify the DNA sequences required for replication origin function in mammalian cells and (ii) to identify the proteins which interact with replication origins to carry out ..
  47. CIS-ACTING DETERMINANTS OF REPLICATION TIMING
    Joel Huberman; Fiscal Year: 2001
    ..94-bp stretch of chromosomal DNA in the budding yeast, Saccharomyces cerevisiae, is capable of serving as a replication origin but differs from previously studied origins in being inherently late replicating...
  48. Monoclonal Antibody Resources for C. elegans
    Michael Nonet; Fiscal Year: 2007
    ..The cellular components include macromolecular complexes (e.g.splicesomes, proteosomes, replication origin complexes) and common cellular proteins (e.gclathrin, kinesin, dynein and intermediate filaments)...
  49. STREPTOCOCCAL MULTIENZYME DNA REPLICATION SYSTEM
    James Bullard; Fiscal Year: 2002
    ..We will also exploit templates containing the Streptococcal replication origin to provide a functional assay for Streptococcal replication and initiation factors...
  50. STRUCTURE AND ACTIVITY OF DNA REPLICATION ORIGINS
    David Kowalski; Fiscal Year: 2004
    ..identified cis-acting DNA elements that are necessary and sufficient to specify and activate a chromosomal replication origin, 0RI305...
  51. MITOCHRONDRIA NUCLEIC ACID SYNTHESIS AND ROLE OF DNA
    MELVIN SIMPSON; Fiscal Year: 1990
    ..4) To study priming activity at the H strand replication origin (located in the D loop region)...
  52. Structure and Function of SV40 Large Tumor Antigen
    DANIEL SIMMONS; Fiscal Year: 2009
    ..abstract_text> ..
  53. AMPLIFICATION--MODEL FOR GENETIC INSTABILITY IN CANCER
    JOYCE HAMLIN; Fiscal Year: 2005
    ..abstract_text> ..
  54. Strategies for mapping origins in mammalian genomes
    JOYCE HAMLIN; Fiscal Year: 2009
    ..By comparing these data to the distributions identified in Aim 1. we will define aspects of chromatin architecture that characterize active origins, origin clusters, and/or local genes. ..
  55. EFFECTS OF CHROMATIN ARCHITECTURE ON ORIGIN ACTIVITY
    PIETER DIJKWEL; Fiscal Year: 2003
    ..role of chromosome architecture, and in particular interaction with the nuclear matrix, in the regulation of replication origin activity in mammalian cells...
  56. Direct analysis of fork blockage and DNA repair in vivo
    Kenneth Kreuzer; Fiscal Year: 2003
    ..If the system is validated, many other kinds of DNA damage can presumably be analyzed in-future studies. ..
  57. DNA Replication during ES Cell Differentiation
    David Gilbert; Fiscal Year: 2004
    ..Conditions for homogeneous differentiation of mES cells will also be applied to hES cells in work aimed at the production of hES cell differentiation intermediates for replication studies. ..
  58. CONJUGATIVE MOBILIZATION OF PLASMID R1162
    Richard Meyer; Fiscal Year: 2003
    ..How pSCl0l has become independent of these proteins will investigated. Overall, these studies will provide insight into how the relaxosome directs plasmid DNA to the conjugal pore for transfer. ..
  59. Biogenesis of Eukaryotic Ribosomes
    SUSAN GERBI; Fiscal Year: 2004
    ..The proposed studies should elucidate the importance of dynamic RNA-RNA interactions during ribosome biogenesis, a fundamental process essential for cell growth and viability. ..
  60. Gene Amplification-Sciarid DNA Puffs
    SUSAN GERBI; Fiscal Year: 2006
    ..Information gained from the unique Sciara system should behelpful in understanding the mechanisms used by metazoa to specify an origin and to regulate its activation. ..