dna replication

Summary

Summary: The process by which a DNA molecule is duplicated.

Top Publications

  1. ncbi ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Shuhei Matsuoka
    Department of Genetics and Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 316:1160-6. 2007
  2. pmc Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Ewan Birney
    Nature 447:799-816. 2007
  3. pmc Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress
    Johnny M Tkach
    Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Nat Cell Biol 14:966-76. 2012
  4. ncbi Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes
    Lee Zou
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 300:1542-8. 2003
  5. pmc Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication
    Agnel Sfeir
    Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Cell 138:90-103. 2009
  6. ncbi Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints
    Aziz Sancar
    Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7260, USA
    Annu Rev Biochem 73:39-85. 2004
  7. ncbi An oncogene-induced DNA damage model for cancer development
    Thanos D Halazonetis
    Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH 1205 Geneva, Switzerland
    Science 319:1352-5. 2008
  8. ncbi Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication
    Raffaella Di Micco
    IFOM Foundation FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy
    Nature 444:638-42. 2006
  9. ncbi Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
    Vassilis G Gorgoulis
    Department of Histology and Embryology, School of Medicine, University of Athens, Athens GR 11527, Greece
    Nature 434:907-13. 2005
  10. ncbi Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK 2100 Copenhagen, Denmark
    Nature 444:633-7. 2006

Detail Information

Publications345 found, 100 shown here

  1. ncbi ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Shuhei Matsuoka
    Department of Genetics and Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 316:1160-6. 2007
    ..This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals...
  2. pmc Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Ewan Birney
    Nature 447:799-816. 2007
    ..Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation...
  3. pmc Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress
    Johnny M Tkach
    Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Nat Cell Biol 14:966-76. 2012
    ..yeast GFP fusion collection to develop a systems-level view of protein reorganization following drug-induced DNA replication stress. Changes in protein localization and abundance reveal drug-specific patterns of functional enrichments...
  4. ncbi Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes
    Lee Zou
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 300:1542-8. 2003
    ..Our data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling...
  5. pmc Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication
    Agnel Sfeir
    Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Cell 138:90-103. 2009
    ..We report that the TTAGGG repeat arrays of mammalian telomeres pose a challenge to the DNA replication machinery, giving rise to replication-dependent defects that resemble those of aphidicolin-induced common ..
  6. ncbi Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints
    Aziz Sancar
    Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7260, USA
    Annu Rev Biochem 73:39-85. 2004
    ..and inactivate cyclin-dependent kinases to inhibit cell cycle progression from G1 to S (the G1/S checkpoint), DNA replication (the intra-S checkpoint), or G2 to mitosis (the G2/M checkpoint)...
  7. ncbi An oncogene-induced DNA damage model for cancer development
    Thanos D Halazonetis
    Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH 1205 Geneva, Switzerland
    Science 319:1352-5. 2008
    ..suggest that, in both precancerous lesions and cancers, activated oncogenes induce stalling and collapse of DNA replication forks, which in turn leads to formation of DNA DSBs...
  8. ncbi Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication
    Raffaella Di Micco
    IFOM Foundation FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy
    Nature 444:638-42. 2006
    ..Senescent cells arrest with partly replicated DNA and with DNA replication origins having fired multiple times...
  9. ncbi Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
    Vassilis G Gorgoulis
    Department of Histology and Embryology, School of Medicine, University of Athens, Athens GR 11527, Greece
    Nature 434:907-13. 2005
    ..skin hyperplasias showed allelic imbalance at loci that are prone to DNA double-strand break formation when DNA replication is compromised (common fragile sites)...
  10. ncbi Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK 2100 Copenhagen, Denmark
    Nature 444:633-7. 2006
    ..One such barrier involves DNA replication stress, which leads to activation of the DNA damage checkpoint and thereby to apoptosis or cell cycle arrest, ..
  11. ncbi The complete genome sequence of Escherichia coli K-12
    F R Blattner
    Laboratory of Genetics, University of Wisconsin Madison, 445 Henry Mall, Madison, WI 53706, USA
    Science 277:1453-62. 1997
    ..The genome also contains insertion sequence (IS) elements, phage remnants, and many other patches of unusual composition indicating genome plasticity through horizontal transfer...
  12. pmc Y-family DNA polymerases and their role in tolerance of cellular DNA damage
    Julian E Sale
    Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Nat Rev Mol Cell Biol 13:141-52. 2012
    ..However, as they exhibit low fidelity when copying undamaged DNA, it is essential that they are only called into play when they are absolutely required. Several layers of regulation ensure that this is achieved...
  13. ncbi 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress
    Claudia Lukas
    Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Nat Cell Biol 13:243-53. 2011
    ..Together, these data indicate that restoration of DNA or chromatin integrity at loci prone to replication problems requires mitotic transmission to the next cell generations...
  14. pmc A chemical method for fast and sensitive detection of DNA synthesis in vivo
    Adrian Salic
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:2415-20. 2008
    ..In contrast to BrdU, the method does not require sample fixation or DNA denaturation and permits good structural preservation. We demonstrate the use of the method in cultured cells and in the intestine and brain of whole animals...
  15. 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
    b>DNA replication initiates from defined locations called replication origins; some origins are highly active, whereas others are dormant and rarely used...
  16. pmc Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair
    Eva Petermann
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, UK
    Mol Cell 37:492-502. 2010
    Faithful DNA replication is essential to all life. Hydroxyurea (HU) depletes the cells of dNTPs, which initially results in stalled replication forks that, after prolonged treatment, collapse into DSBs...
  17. 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
    b>DNA replication is highly regulated, ensuring faithful inheritance of genetic information through each cell cycle...
  18. pmc DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase
    Katrin Paeschke
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Cell 145:678-91. 2011
    ..was relieved by spontaneous mutations that eliminated their ability to form G4 structures, bind Pif1, slow DNA replication, and stimulate DNA breakage...
  19. ncbi Maintaining genome stability at the replication fork
    Dana Branzei
    Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM IEO Campus, Via Adamello 16, 20139 Milan, Italy
    Nat Rev Mol Cell Biol 11:208-19. 2010
    Aberrant DNA replication is a major source of the mutations and chromosome rearrangements that are associated with pathological disorders. When replication is compromised, DNA becomes more prone to breakage...
  20. pmc Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress
    Alberto Ciccia
    Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA
    Mol Cell 47:396-409. 2012
    Completion of DNA replication after replication stress depends on PCNA, which undergoes monoubiquitination to stimulate direct bypass of DNA lesions by specialized DNA polymerases or is polyubiquitinated to promote recombination-..
  21. pmc Kinetochores coordinate pericentromeric cohesion and early DNA replication by Cdc7-Dbf4 kinase recruitment
    Toyoaki Natsume
    Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Mol Cell 50:661-74. 2013
    ..Thus, we have found the central mechanism by which kinetochores orchestrate early S phase DNA replication and robust sister chromatid cohesion at microtubule attachment sites.
  22. ncbi Genome instability: a mechanistic view of its causes and consequences
    Andres Aguilera
    Centro Andaluz de Biologia Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla CSIC, Avd Américo Vespucio s n, 41092 Sevilla, Spain
    Nat Rev Genet 9:204-17. 2008
    ..Taking these elements as a guide, we review the causes and consequences of instability with the aim of providing a mechanistic perspective on the origin of genomic instability...
  23. ncbi Pathways of mammalian replication fork restart
    Eva Petermann
    University of Birmingham, UK
    Nat Rev Mol Cell Biol 11:683-7. 2010
    Single-molecule analyses of DNA replication have greatly advanced our understanding of mammalian replication restart...
  24. pmc Proliferating cell nuclear antigen (PCNA): a key factor in DNA replication and cell cycle regulation
    Wojciech Strzalka
    Department of Plant Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Krakow, Poland
    Ann Bot 107:1127-40. 2011
    ..of yeast, plant and animal cells that undergo cell division, suggesting a function in cell cycle regulation and/or DNA replication. It subsequently became clear that PCNA also played a role in other processes involving the cell genome.
  25. pmc Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types
    Tyrone Ryba
    Department of Biological Science, Florida State University, Tallahassee, Florida 32306, USA
    Genome Res 20:761-70. 2010
    ....
  26. ncbi Collisions between replication and transcription complexes cause common fragile site instability at the longest human genes
    Anne Helmrich
    Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS UMR 7104, INSERM U 964, Universite de Strasbourg, BP 10142 67404 Illkirch Cedex, France
    Mol Cell 44:966-77. 2011
    ..Functional replication machinery needs to be involved in the resolution of conflicts between transcription and replication machineries to ensure genomic stability...
  27. ncbi Expandable DNA repeats and human disease
    Sergei M Mirkin
    Department of Biology, Tufts University, Medford, Massachusetts 02155, USA
    Nature 447:932-40. 2007
    ..It is becoming clear that the peculiar structures of repeat-containing transcripts are at the heart of the pathogenesis of these diseases...
  28. ncbi DNA double-strand break repair: from mechanistic understanding to cancer treatment
    Thomas Helleday
    Radiation Oncology and Biology, University of Oxford, Oxford OX3 7LJ, UK
    DNA Repair (Amst) 6:923-35. 2007
    ....
  29. 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...
  30. pmc A microhomology-mediated break-induced replication model for the origin of human copy number variation
    P J Hastings
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS Genet 5:e1000327. 2009
    ....
  31. ncbi Dynamics of replication-independent histone turnover in budding yeast
    Michael F Dion
    Faculty of Arts and Sciences, Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA
    Science 315:1405-8. 2007
    ..In addition, rapid histone turnover is found at known chromatin boundary elements. These results suggest that rapid histone turnover serves to functionally separate chromatin domains and prevent spread of histone states...
  32. pmc Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair
    Jennifer M Svendsen
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 138:63-77. 2009
    ..Thus, SLX4 assembles a modular toolkit for repair of specific types of DNA lesions and is critical for cellular responses to replication fork failure...
  33. ncbi Common fragile sites: mechanisms of instability revisited
    Michelle Debatisse
    Institut Curie, Centre de Recherche, 26 Rue d Ulm, 75248 Paris, France
    Trends Genet 28:22-32. 2012
    ..However, recent studies show that delayed completion of DNA replication instead depends on a regional paucity in initiation events...
  34. ncbi Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis
    Marzena Bienko
    Institute for Biochemistry II, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Science 310:1821-4. 2005
    ..Our results indicate that Ub-binding domains of Y-family polymerases play crucial regulatory roles in TLS...
  35. pmc Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements
    Pengfei Liu
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Cell 146:889-903. 2011
    ..The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle...
  36. pmc Mitochondrial DNA mutations in disease and aging
    Chan Bae Park
    Institute for Medical Sciences, Ajou University School of Medicine, Suwon 443 721, Korea
    J Cell Biol 193:809-18. 2011
    ..In addition, mounting evidence suggests that most mtDNA mutations may be generated by replication errors and not by accumulated damage...
  37. pmc Human mutation rate associated with DNA replication timing
    John A Stamatoyannopoulos
    Department of Genome Sciences and Medicine, University of Washington, Seattle, WA, USA
    Nat Genet 41:393-5. 2009
    Eukaryotic DNA replication is highly stratified, with different genomic regions shown to replicate at characteristic times during S phase...
  38. pmc Nucleotide deficiency promotes genomic instability in early stages of cancer development
    Assaf C Bester
    Department of Genetics, The Life Sciences Institute, Edmond J Safra Campus, The Hebrew University, Jerusalem, Israel
    Cell 145:435-46. 2011
    Chromosomal instability in early cancer stages is caused by stress on DNA replication. The molecular basis for replication perturbation in this context is currently unknown...
  39. ncbi (p)ppGpp: still magical?
    Katarzyna Potrykus
    Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2785, USA
    Annu Rev Microbiol 62:35-51. 2008
    ..Many basic questions still exist. This review tries to focus on some issues that linger even for the most widely characterized bacterial strains...
  40. pmc Endogenous DNA replication stress results in expansion of dNTP pools and a mutator phenotype
    Marta B Davidson
    Department of Biochemistry and Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
    EMBO J 31:895-907. 2012
    ..Together, our data point to a vicious circle in which mutations in gatekeeper genes give rise to genomic instability during S phase, inducing expansion of the dNTP pool, which in turn results in high levels of spontaneous mutagenesis...
  41. pmc A distinct replication fork protection pathway connects Fanconi anemia tumor suppressors to RAD51-BRCA1/2
    Katharina Schlacher
    Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cancer Cell 22:106-16. 2012
    ..Collective results imply a unified molecular mechanism for repair-independent functions of FA, RAD51, and BRCA1/2 proteins in preventing genomic instability and suppressing tumorigenesis...
  42. pmc Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing
    Dirk Remus
    Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms EN6 3LD, UK
    Cell 139:719-30. 2009
    The licensing of eukaryotic DNA replication origins, which ensures once-per-cell-cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs)...
  43. pmc Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint
    Tony S Byun
    Department of Molecular Pharmacology, Stanford University, Stanford, CA 94305, USA
    Genes Dev 19:1040-52. 2005
    ..ATR-dependent DNA damage response pathway can respond to a diverse group of lesions as well as inhibitors of DNA replication. Using the Xenopus egg extract system, we show that lesions induced by UV irradiation and cis-platinum cause ..
  44. pmc Sequencing newly replicated DNA reveals widespread plasticity in human replication timing
    R Scott Hansen
    Department of Medicine, Division of Medical Genetics, University of Washington School of Medicine, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 107:139-44. 2010
    Faithful transmission of genetic material to daughter cells involves a characteristic temporal order of DNA replication, which may play a significant role in the inheritance of epigenetic states...
  45. ncbi Chromatin replication and epigenome maintenance
    Constance Alabert
    Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, DK2200 Copenhagen, Denmark
    Nat Rev Mol Cell Biol 13:153-67. 2012
    ..Chromatin and nuclear structure influence where and when DNA replication initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of ..
  46. ncbi Differential timing and control of noncrossover and crossover recombination during meiosis
    T Allers
    Laboratory of Biochemistry, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Cell 106:47-57. 2001
    ..These results suggest that crossovers are formed by resolution of Holliday junction intermediates, while most noncrossover recombinants arise by a different, earlier pathway...
  47. 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...
  48. ncbi PCNA, the maestro of the replication fork
    George Lucian Moldovan
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18 82152 Martinsried, Germany
    Cell 129:665-79. 2007
    ..Switching of PCNA partners may be triggered by affinity-driven competition, phosphorylation, proteolysis, and modification of PCNA by ubiquitin and SUMO...
  49. pmc DNA replication timing and long-range DNA interactions predict mutational landscapes of cancer genomes
    Subhajyoti De
    Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Nat Biotechnol 29:1103-8. 2011
    ..Here we integrate data on DNA replication timing, long-range interactions between genomic material, and 331,724 SCNAs from 2,792 cancer samples ..
  50. pmc Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11
    Katharina Schlacher
    Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 145:529-42. 2011
    ..Thus, BRCA2 prevents rather than repairs nucleolytic lesions at stalled replication forks to maintain genomic integrity and hence likely suppresses tumorigenesis through this replication-specific function...
  51. pmc A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability
    Renee D Paulsen
    Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA
    Mol Cell 35:228-39. 2009
    ..These data indicate that preservation of genome stability is mediated by a larger network of biological processes than previously appreciated...
  52. ncbi Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism
    M S Wold
    Department of Biochemistry, University of Iowa College of Medicine, Iowa City 52242, USA
    Annu Rev Biochem 66:61-92. 1997
    ..DNA-binding protein that is required for multiple processes in eukaryotic DNA metabolism, including DNA replication, DNA repair, and recombination...
  53. ncbi DNA damage checkpoints: from initiation to recovery or adaptation
    Jiri Bartek
    Department of Cell Cycle and Cancer, and Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Curr Opin Cell Biol 19:238-45. 2007
    ..Such studies highlight the dynamic nature of these processes and help us to better understand the molecular basis, spatiotemporal orchestration and biological significance of the DNA damage response in normal and cancerous cells...
  54. ncbi Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion
    Tom Rolef Ben-Shahar
    Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln sInn Fields, London WC2A 3PX, UK
    Science 321:563-6. 2008
    ..Eco1 dispensable for cell growth, and we show that Smc3 is acetylated in an Eco1-dependent manner during DNA replication to promote sister chromatid cohesion...
  55. ncbi Epigenetic inheritance during the cell cycle
    Aline V Probst
    Laboratory of Nuclear Dynamics and Genome Plasticity, UMR218 Centre National de la Recherche Scientifique Institut Curie, 26, rue d Ulm, 75231 Paris Cedex 05, France
    Nat Rev Mol Cell Biol 10:192-206. 2009
    Studies that concern the mechanism of DNA replication have provided a major framework for understanding genetic transmission through multiple cell cycles...
  56. pmc The complete genome of the crenarchaeon Sulfolobus solfataricus P2
    Q She
    Microbial Genome Group, Institute of Molecular Biology, University of Copenhagen, , DK-1307 Copenhagen, Denmark
    Proc Natl Acad Sci U S A 98:7835-40. 2001
    ..The essential components required for DNA replication, DNA repair and recombination, the cell cycle, transcriptional initiation and translation, but not DNA ..
  57. pmc The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome
    Alex J Kuo
    Department of Biology, Stanford University, Stanford, California 94305, USA
    Nature 484:115-9. 2012
    ..repair; however, no effector functions have yet been identified within the mammalian machinery that regulate DNA replication. Here we show that ORC1--a component of ORC (origin of replication complex), which mediates pre-DNA ..
  58. ncbi Topoisomerase I poisoning results in PARP-mediated replication fork reversal
    Arnab Ray Chaudhuri
    Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
    Nat Struct Mol Biol 19:417-23. 2012
    Topoisomerase I (Top1) releases torsional stress during DNA replication and transcription and is inhibited by camptothecin and camptothecin-derived cancer chemotherapeutics...
  59. ncbi DNA replication and transcription in mammalian mitochondria
    Maria Falkenberg
    Division of Metabolic Diseases, Karolinska Institutet, Novum, SE 141 86 Stockholm
    Annu Rev Biochem 76:679-99. 2007
    ..This observation has led to the proposition that some genes required for DNA replication and transcription were acquired together from a phage early in the evolution of the eukaryotic cell, already ..
  60. ncbi Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects
    Jose M Sogo
    Institute of Cell Biology, ETH Honggerberg, CH 8093 Zurich, Switzerland
    Science 297:599-602. 2002
    ..We speculate that, in checkpoint mutants, abnormal replication intermediates begin to form because of uncoordinated replication and are further processed by unscheduled recombination pathways, causing genome instability...
  61. ncbi Activation of the MCM2-7 helicase by association with Cdc45 and GINS proteins
    Ivar Ilves
    Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Mol Cell 37:247-58. 2010
    MCM2-7 proteins provide essential helicase functions in eukaryotes at chromosomal DNA replication forks. During the G1 phase of the cell cycle, they remain loaded on DNA but are inactive...
  62. 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
    Chromosomal DNA replication in eukaryotes initiates from multiple origins of replication, and because of this multiplicity, activation of replication origins is likely to be highly coordinated; origins fire at characteristic times, with ..
  63. 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
    At each cell division in humans, 30,000-50,000 DNA replication origins are activated, and it remains unclear how they are selected and recognized by replication factors...
  64. 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
    b>DNA replication is central to cell proliferation...
  65. 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
    ..Such obstacles can be called natural impediments to DNA replication, as opposed to external and genetic factors...
  66. pmc Break-induced replication is highly inaccurate
    Angela Deem
    Department of Biology, School of Science, IUPUI, Indianapolis, Indiana, United States of America
    PLoS Biol 9:e1000594. 2011
    ..Break-induced replication (BIR) is a unique cellular process that mimics normal DNA replication in its processivity, rate, and capacity to duplicate hundreds of kilobases, but is initiated at double-strand ..
  67. pmc A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging
    Matilde Murga
    Genomic Instability Group, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    Nat Genet 41:891-8. 2009
    ....
  68. pmc Location, location, location: it's all in the timing for replication origins
    Oscar M Aparicio
    Molecular and Computational Biology Program, University of Southern California, Los Angeles, California 90089, USA
    Genes Dev 27:117-28. 2013
    ..The mechanisms that control the spatial organization of replication origins have potential impacts for genome regulation beyond replication...
  69. pmc Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei
    Calvin Tiengwe
    The Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK
    Cell Rep 2:185-97. 2012
    ..To understand how DNA replication occurs in the context of such organization, we have performed genome-wide mapping of the binding sites of the ..
  70. 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
    In metazoans, thousands of DNA replication origins (Oris) are activated at each cell cycle. Their genomic organization and their genetic nature remain elusive...
  71. pmc Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome
    Avvaru N Suhasini
    Laboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, Baltimore, MD 21224, USA
    EMBO J 30:692-705. 2011
    ..Collectively, the results suggest that FANCJ catalytic activity and its effect on BLM protein stability contribute to preservation of genomic stability and a normal response to replication stress...
  72. pmc R-loop-mediated genomic instability is caused by impairment of replication fork progression
    Wenjian Gan
    College of Life Sciences, Peking University, Beijing 100871, China
    Genes Dev 25:2041-56. 2011
    ..More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability...
  73. ncbi Sororin mediates sister chromatid cohesion by antagonizing Wapl
    Tomoko Nishiyama
    Research Institute of Molecular Pathology, Vienna, Austria
    Cell 143:737-49. 2010
    ..We show that DNA replication and cohesin acetylation promote binding of Sororin to cohesin, and that Sororin displaces Wapl from its ..
  74. ncbi Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map
    Sean R Collins
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA
    Nature 446:806-10. 2007
    ..between 743 Saccharomyces cerevisiae genes involved in various aspects of chromosome biology (including DNA replication/repair, chromatid segregation and transcriptional regulation)...
  75. pmc A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability
    Zhijiang Yan
    Laboratory of Genetics, National Institute of Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Mol Cell 37:865-78. 2010
    FANCM remodels branched DNA structures and plays essential roles in the cellular response to DNA replication stress. Here, we show that FANCM forms a conserved DNA-remodeling complex with a histone-fold heterodimer, MHF...
  76. pmc The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair
    Puck Knipscheer
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Science 326:1698-701. 2009
    ..Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised...
  77. pmc Polymerase dynamics at the eukaryotic DNA replication fork
    Peter M J Burgers
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 284:4041-5. 2009
    This review discusses recent insights in the roles of DNA polymerases (Pol) delta and epsilon in eukaryotic DNA replication. A growing body of evidence specifies Pol epsilon as the leading strand DNA polymerase and Pol delta as the ..
  78. pmc The Mcm complex: unwinding the mechanism of a replicative helicase
    Matthew L Bochman
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    Microbiol Mol Biol Rev 73:652-83. 2009
    ..replicative helicase, the molecular motor that both unwinds duplex DNA and powers fork progression during DNA replication. Consistent with its central role in this process, much prior work has illustrated that Mcm2-7 loading and ..
  79. pmc Collaboration and competition between DNA double-strand break repair pathways
    Elizabeth M Kass
    Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    FEBS Lett 584:3703-8. 2010
    ....
  80. pmc Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer
    Michael M Vilenchik
    The Sally Balin Medical Center, Media, PA 19063, USA
    Proc Natl Acad Sci U S A 100:12871-6. 2003
    ..We conclude that rates of production of EDSBs and of ensuing spontaneous mitotic recombination events can account for a substantial fraction of the earliest oncogenic events in human carcinomas...
  81. ncbi Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM
    Alberto Ciccia
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK
    Mol Cell 25:331-43. 2007
    ..Our data indicate that the FANCM/FAAP24 complex may play a key role in recruitment of the FA core complex to damaged DNA...
  82. ncbi Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis
    Hideaki Tagami
    Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Cell 116:51-61. 2004
    Deposition of the major histone H3 (H3.1) is coupled to DNA synthesis during DNA replication and possibly DNA repair, whereas histone variant H3.3 serves as the replacement variant for the DNA-synthesis-independent deposition pathway...
  83. pmc PCNA directs type 2 RNase H activity on DNA replication and repair substrates
    Doryen Bubeck
    Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK
    Nucleic Acids Res 39:3652-66. 2011
    ..syndrome, an auto-inflammatory disorder that may arise from nucleic acid byproducts generated during DNA replication. Here, we report the crystal structures of Archaeoglobus fulgidus RNase HII in complex with PCNA, and human ..
  84. pmc Stalled fork rescue via dormant replication origins in unchallenged S phase promotes proper chromosome segregation and tumor suppression
    Tsuyoshi Kawabata
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA
    Mol Cell 41:543-53. 2011
    Eukaryotic cells license far more origins than are actually used for DNA replication, thereby generating a large number of dormant origins...
  85. pmc Ubiquitin-dependent DNA damage bypass is separable from genome replication
    Yasukazu Daigaku
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK
    Nature 465:951-5. 2010
    Post-replication repair (PRR) is a pathway that allows cells to bypass or overcome lesions during DNA replication. In eukaryotes, damage bypass is activated by ubiquitylation of the replication clamp PCNA through components of the RAD6 ..
  86. 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...
  87. ncbi Eukaryotic DNA replication control: lock and load, then fire
    Dirk Remus
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, UK
    Curr Opin Cell Biol 21:771-7. 2009
    The initiation of chromosomal DNA replication involves initiator proteins that recruit and load hexameric DNA helicases at replication origins. This helicase loading step is tightly regulated in bacteria and eukaryotes...
  88. ncbi FANCM connects the genome instability disorders Bloom's Syndrome and Fanconi Anemia
    Andrew J Deans
    London Research Institute, Cancer Research UK, South Mimms, UK
    Mol Cell 36:943-53. 2009
    ..Moreover, a common phenotype of BS and FA cells-an elevated frequency of sister chromatid exchanges-was due to a loss of interaction of the two complexes through FANCM...
  89. pmc High efficiency mutagenesis, repair, and engineering of chromosomal DNA using single-stranded oligonucleotides
    H M Ellis
    Gene Regulation and Chromosome Biology Laboratory, Division of Basic Sciences, National Cancer Institute at Frederick, P.O. Box B, Frederick, MD 21702, USA
    Proc Natl Acad Sci U S A 98:6742-6. 2001
    ..protein, a Rad52-like protein, binds and anneals the ssDNA donor to a complementary single-strand near the DNA replication fork to generate the recombinant...
  90. 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
    Origins of DNA replication must be regulated to ensure that the entire genome is replicated precisely once in each cell cycle...
  91. ncbi Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A
    Claus Storgaard Sørensen
    Danish Cancer Society, Institute of Cancer Biology, Strandboulevarden 49, DK 2100 Copenhagen Ø, Denmark
    Cancer Cell 3:247-58. 2003
    ..Our results provide evidence that the mammalian S phase checkpoint functions via amplification of physiologically operating, Chk1-dependent mechanisms...
  92. pmc ATR activation and replication fork restart are defective in FANCM-deficient cells
    Rebekka A Schwab
    Department of Molecular Oncology, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK
    EMBO J 29:806-18. 2010
    ..Our data therefore indicate a fundamental role for FANCM in the maintenance of genome integrity during S phase...
  93. ncbi The checkpoint response to replication stress
    Dana Branzei
    FIRC Institute of Molecular Oncology Foundation IFOM IEO campus, Via Adamello 16, 20139 Milan, Italy
    DNA Repair (Amst) 8:1038-46. 2009
    Genome instability is a hallmark of cancer cells, and defective DNA replication, repair and recombination have been linked to its etiology...
  94. 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
    ..and a key feature of this process is the activation of the replicative DNA helicase in situ at each origin of DNA replication. A series of recent studies has shed new light on the targets of Cdc7 and CDK, indicating that chromosome ..
  95. ncbi Replication stress induces sister-chromatid bridging at fragile site loci in mitosis
    Kok Lung Chan
    Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK
    Nat Cell Biol 11:753-60. 2009
    ..Similarly to fragile site expression, fragile site bridging is induced after partial inhibition of DNA replication. We propose that, after replication stress, sister chromatids are interlinked by replication intermediates ..
  96. pmc Nearby inverted repeats fuse to generate acentric and dicentric palindromic chromosomes by a replication template exchange mechanism
    Ken Ichi Mizuno
    Genome Damage and Stability Centre, University of Sussex, Brighton Sussex BN1 9RQ, United Kingdom
    Genes Dev 23:2876-86. 2009
    ..We thus propose an alternative mechanism for the generation of palindromic chromosomes dependent on replication fork arrest at closely spaced inverted repeats...
  97. pmc Roles of Werner syndrome protein in protection of genome integrity
    Marie L Rossi
    Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA
    DNA Repair (Amst) 9:331-44. 2010
    ..WRN is one of the best characterized of the RecQ helicases and is known to have roles in DNA replication and repair, transcription, and telomere maintenance...
  98. ncbi Genome-wide replication-independent histone H3 exchange occurs predominantly at promoters and implicates H3 K56 acetylation and Asf1
    Anne Rufiange
    Centre de recherche en cancérologie de l Université Laval, L Hôtel Dieu de Québec CHUQ, Quebec, Canada
    Mol Cell 27:393-405. 2007
    ..Taken together, our data underline the dynamic nature of replication-independent nucleosome assembly/disassembly, specify a link to transcription, and implicate Asf1 and H3 K56 acetylation...
  99. ncbi The RAD6 DNA damage tolerance pathway operates uncoupled from the replication fork and is functional beyond S phase
    Georgios I Karras
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Cell 141:255-67. 2010
    ..We therefore propose that the RAD6 pathway acts on single-stranded gaps left behind newly restarted replication forks...
  100. 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
    Many of the factors required for chromosomal DNA replication have been identified in unicellular eukaryotes. However, DNA replication is poorly understood in multicellular organisms...
  101. pmc The S-phase checkpoint is required to respond to R-loops accumulated in THO mutants
    Belén Gómez-González
    Centro Andaluz de Biologia Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla CSIC, Av Americo Vespucio s n, 41092 Seville, Spain
    Mol Cell Biol 29:5203-13. 2009
    ..In light of these results, we propose a model in which R-loop-mediated recombination is explained by template switching...

Research Grants67

  1. Optimization of DNA Repair by Abh8
    Lauren Endres; Fiscal Year: 2013
    ..To ensure fidelity during DNA replication, the repair of single and double strand breaks is critical for genome maintenance and chromosome stability...
  2. Regulation of HSV-1 Gene Expression and Replication by Nuclear Hormone Receptors
    SHAOCHUNG VICTOR HSIA; Fiscal Year: 2013
    ..supported by the literature and our observations: First, HSV-1 TK and ICP0 are important for efficient viral DNA replication and transcription within the infected neurons. Second, TR is present in sensory ganglia...
  3. Med1 in Liver Metabolism, Regeneration and Cancer
    Janardan K Reddy; Fiscal Year: 2013
    ..showing that adenovirally-driven overexpression of Med1 (adeno-Med1) in mouse liver stimulates hepatocyte DNA replication and regeneration...
  4. Molecular Mechanisms of Parvovirus Gene Expression and Replication
    Jianming Qiu; Fiscal Year: 2013
    ..by the erythropoietin receptor to the Ras/MEK/ERK pathway in EPCs, and plays an important role in viral DNA replication. Importantly, B19V infection induces a DNA damage response (DDR)...
  5. Environmental Risk Factors for Copy Number Variation in Human Chromosomes
    THOMAS EDWARD WILSON; Fiscal Year: 2010
    ..majority of disease-associated CNVs in humans and those in cancers arise via mechanisms coupled to aberrant DNA replication and/or non-homologous repair of DNA damage...
  6. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2013
    ..Our latest results showed that Tax caused significant accumulation of the DNA replication licensing factor, Cdt1, during S/G2...
  7. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
    ..DNA lesions arise as a consequence of both endogenous cellular processes such as metabolic reactions and DNA replication, and through exposure of cells to environmental mutagens including chemical carcinogens, UV light and gamma-..
  8. The Role of MYST Histone Acetyltransferase in Genome Stability
    M Mitchell Smith; Fiscal Year: 2013
    ..Based on our work and that of others, it is clear that Myst2 is required for DNA replication licensing, interacts with p53 to mediate stress signaling, and has roles in transcription...
  9. Hepatitis B virus replication and DDB1
    Betty L Slagle; Fiscal Year: 2013
    ..In this manner, DDB1 regulates diverse cellular functions such as DNA replication, cell cycle, innate immunity, and damaged DNA repair...
  10. Integrating stress MAP kinase signaling with DNA replication origin licensing
    Jeanette Gowen Cook; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Timely, complete, and precise DNA replication followed by accurate chromosome segregation is critical for controlling cell proliferation and genome stability...
  11. Regulation of EBV Latency by EBNA1
    Paul M Lieberman; Fiscal Year: 2013
    ..EBNA1 is a multifunctional, sequence-specific DNA-binding protein that regulates viral DNA replication, episome maintenance, metaphase chromosome tethering, and transcription...
  12. The role of LKB1 in the maintenance of genomic stability.
    Zhi Xiang Xu; Fiscal Year: 2013
    ..Hypothesis to be tested: LKB1 is a DDR protein that regulates the enzymes involved in DNA-damage repair and DNA replication. As a corollary, loss of LKB1 may lead to an accumulation of DNA damage, an increase in genomic instability, ..
  13. Inactivation of Hdac3 in the cause, prevention, and treatment of HCC
    Scott W Hiebert; Fiscal Year: 2013
    ..damage that was most likely due to inefficient repair of the DNA double strand breaks that occur at stalled DNA replication forks. We have now begun to translate this information to the in vivo requirements for Hdac3 in adult mice...
  14. Metnase, PIKK, and RPA Roles in DNA Damage and Replication Stress Responses
    Jac A Nickoloff; Fiscal Year: 2013
    ..by applicant): Most cancer patients receive radio- and/or chemotherapy that causes DNA damage, which blocks DNA replication. Normal and tumor cells respond to DNA damage and associated replication stress by activating DNA repair, ..
  15. Roles of the mammalian CST complex in DNA replication and chromosome cohesion
    JASON AARON STEWART; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): There is a fundamental gap in our current understanding of how DNA replication proceeds through naturally occurring barriers and how sister chromatid cohesion (SCC) is established during DNA ..
  16. The Role of the Nuclear Lamina in Chromatin Organization and Gene Expression in N
    Marcos Estecio; Fiscal Year: 2012
    ..This structure has activity in key cellular functions, such as DNA replication, cell division and apoptosis...
  17. A common denominator of pathogenesis;a rare opportunity for novel therapeutic de
    DOUGLAS ALAN MITCHELL; Fiscal Year: 2011
    ..our perspective, new antimicrobial strategies should directly target the pathogenic mechanism, rather than DNA replication, protein synthesis, or the cell wall...
  18. Evaluation of a new class of antimicrobial agents against Clostridium difficile
    SAUL R contact TZIPORI; Fiscal Year: 2011
    ..MBX 259C, the prototype drug, is a dual acting DNA replication inhibitor which targets DNA polymerase through its anilino uracil (AU) component and gyrase/topoisomerase ..
  19. Role of Polo-like kinase (Plk-1) in Hepatitis B Virus-mediated Hepatocellular Car
    Ourania M Andrisani; Fiscal Year: 2010
    ..We identified genes involved in 1) DNA replication and mitotic progression, 2) DNA repair and 3) p53 function...
  20. CYCLE REGULATION IN THE SYMBIONT SINORHIZOBIUM MELILOTI
    KATHERINE ELISABETH GIBSON; Fiscal Year: 2011
    ..Our flow cytometry results further demonstrate that each HK mutant is unable to properly coordinate DNA replication initiation with cytokinesis...
  21. The role of human DNA polymerase eta in the mutagenic response to oxidative stres
    SCOTT DAVID MCCULLOCH; Fiscal Year: 2013
    ..Translesion synthesis (TLS) by specialized polymerases of the Y-family is therefore a necessary component of DNA replication. Direct bypass of damage allows completion of DNA replication in the face of lesions that would otherwise ..
  22. Mechanisms of arsenic-induced chromosomal instability and carcinogenesis
    Wei Dai; Fiscal Year: 2013
    ..High fidelity DNA replication and faithful distribution of the chromosomal complement to daughter cells during cell division are of ..
  23. GENETIC APPROACHES TO PROTEIN-NUCLEIC ACID INTERACTIONS
    Paul R Schimmel; Fiscal Year: 2012
    ..showed that editing defects are mutagenic in aging bacteria, because of mistranslation of proteins in the DNA replication apparatus, including the DNA repair systems...
  24. CSHL Eukaryotic DNA Replication Conference
    David J Stewart; Fiscal Year: 2013
    DESCRIPTION (provided by applicant):: 2013 CONFERENCE ON EUKARYOTIC DNA REPLICATION &GENOME MAINTENANCE This conference will be the 14th biennial meeting on Eukaryotic DNA Replication and Genome Maintenance and follows the highly ..
  25. INTERNATIONAL HERPESVIRUS WORKSHOP
    Jay A Nelson; Fiscal Year: 2012
    ..virus structure, mechanism of virus entry and cell-cell spread, membrane proteins, pathogenesis and latency, DNA replication, vaccination and the immune response, transcriptional control, regulation of gene expression, ..
  26. Checkpoints and double strand breaks in S. pombe meiosis
    Susan L Forsburg; Fiscal Year: 2013
    ..Maintenance of genome stability during the normal cell cycle is closely tied to DNA replication fork stability and repair...
  27. Glucose energy metabolism in the growth and survival of B lymphocytes
    THOMAS CRANE CHILES; Fiscal Year: 2010
    ..via induction of glucose 6-phosphate dehydrogenase (G6PD) gene expression) to support B-cell growth and DNA replication, respectively...
  28. Function of mRNA Editing in Trypanosomes
    Stephen L Hajduk; Fiscal Year: 2010
    ..mutants to evaluate the role of AEP-1 within the tripartite attachment complex (TAC) in kinetoplast DNA replication and proteomic analysis to identify associated proteins and in vitro DNA binding studies to further explore ..
  29. E2-Cellular Complexes in HPV Chromatin Transcription
    Cheng Ming Chiang; Fiscal Year: 2013
    ..Since early protein 2 (E2) encoded by HPVs is crucial for viral DNA replication, HPV genome segregation, control of viral gene expression, and induction of cellular apoptosis and senescence,..
  30. 2011 Nucleic Acids Gordon Research Conference
    Christopher D Lima; Fiscal Year: 2011
    ..Specific topics include: Genome Integrity;DNA Replication;Transcription and Chromatin Dynamics;Co- and Post-transcriptional Regulation;Non-coding RNA;RNA Stability and ..
  31. 2011 EUKARYOTIC DNA REPLICATION &GENOME MAINTENANCE
    David J Stewart; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): This conference will be the 13th biennial meeting on Eukaryotic DNA Replication and Genome Maintenance and follows the highly successful meetings that have been held at Cold Spring Harbor every ..
  32. Agnoprotein in JC virus virion biogenesis and replication
    Mahmut Safak; Fiscal Year: 2012
    ..mechanisms by which agnoprotein regulates both the virion formation and large T antigen-mediated viral DNA replication;and ii) examine the impact of both PP2A and Sm t-Ag on agnoprotein functions during this process...
  33. INTERNATIONAL HERPESVIRUS WORKSHOP
    Jay A Nelson; Fiscal Year: 2011
    ..virus structure, mechanism of virus entry and cell-cell spread, membrane proteins, pathogenesis and latency, DNA replication, vaccination and the immune response, transcriptional control, regulation of gene expression, ..
  34. CELL CYCLE CONTROL IN EARLY DROSOPHILA DEVELOPMENT
    Terry L Orr-Weaver; Fiscal Year: 2013
    ..completion of meiosis, the modified cell cycle used to produce haploid eggs and sperm, and the activation of DNA replication and mitosis in the zygote that results from fusion of sperm and egg...
  35. Mechanistic validation of SCF E3 ligase as a cancer and radiosensitizing target
    Yi Sun; Fiscal Year: 2013
    ..thus governing important biological processes, including cell cycle progression, signal transduction and DNA replication. While cullin-ROC constitutes the core ligase component, cullin needs to be neddylated via Nedd8-Activating ..
  36. HTLV-I Tax activates the anaphase promoting complex
    Chou Zen Giam; Fiscal Year: 2013
    ..The aberrant DNA replication (re-/hyper-replication) in turn causes multinucleation, double-stranded DNA breaks and DNA damage checkpoint ..
  37. Contribution of Sperm Nucleus to Paternal DNA Replication
    WILLIAM S WARD; Fiscal Year: 2013
    ..nucleus provides molecular components that are essential for the proper initiation and regulation of paternal DNA replication. Without these elements, our published data suggest that the paternal DNA would never be replicated, and ..
  38. Development of Novel Agents Targeting Genome Stability and Maintenance for Treati
    John J Turchi; Fiscal Year: 2013
    ..and carboplatin both impart their chemotherapeutic effect by the formation of Pt-DNA adducts which block DNA replication and transcription culminating in apoptosis...
  39. Analysis of the Human c-myc Gene Replication Origin
    Michael Leffak; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Inappropriate regulation of DNA replication initiation can lead to chromosome fragmentation, abnormal cell division and human disease...
  40. Glypican-1 in gliomagenesis
    Andreas Friedl; Fiscal Year: 2013
    ..These coordinated changes in cell cycle regulators lead to G1-S-transition and DNA replication. In glioma cells and astrocytes, GPC1 overexpression also induces DNA re-replication resulting in DNA damage...
  41. Kinetics of DNA polymerase gamma upon mutation and nucleoside analog exposure
    CHRISTAL DYANE SOHL; Fiscal Year: 2013
    ..3 also can use these nucleoside analogs as substrates, resulting in chain termination during mitochondrial DNA replication. Symptoms similar to those seen in progressive external ophthalmoplegia can result, as well as lactic ..
  42. HTS assay development targeting Yersinia pestis topoisomerase I
    Yuk Ching Tse-Dinh; Fiscal Year: 2011
    ..Bacterial topoisomerase I affects global and local DNA supercoiling influencing DNA replication, transcription, recombination and repair...
  43. RNA Polymerase Transcription Past DNA Adducts
    David A Scicchitano; Fiscal Year: 2013
    ..This research shifts the long-standing emphasis from the effects of DNA lesions on DNA replication, which is important in cells undergoing growth and division, to the role DNA damage plays in RNA synthesis, a ..
  44. Validation and Development of WEE1 as a therapeutic target in AML
    Christopher C Porter; Fiscal Year: 2013
    ..project is that Wee1 is a critical mediator of leukemia cell survival, acting inS phase to ensure accurate DNA replication, and that combining inhibition of Wee1 with antimetabolites will be more effective in eliminating leukemia ..
  45. LANA and Cellular Gene Expression
    ROLF F RENNE; Fiscal Year: 2013
    ..protein, which regulates host and viral gene expression and is the only viral protein required for latent DNA replication and episome segregation during latency...
  46. The Molecular Mechanisms by which the Paf Oncogene Mediates Hematopoiesis
    Lisa K Denzin; Fiscal Year: 2013
    ..PCNA has essential roles in multiple processes, such as DNA replication and repair, cell cycle control, chromatin remodeling, epigenetic inheritance, sister chromatid cohesion, and ..
  47. Direct Regulation of Mitochondrial Transcription by Thyroid Hormone and Receptor
    MEGAN LYNN BESTWICK; Fiscal Year: 2012
    ..These are unique organelles in that they house their own mitochondrial genome (mtDNA) as well as their own DNA replication, transcription and translation enzymes...
  48. Functional analysis of Chk2 in DNA damage response
    Jun Hyun Kim; Fiscal Year: 2013
    ..Rad53 regulates DNA replication through its functions in transcription, inhibition of origin firing and stabilization of replication fork...
  49. Regulation of chromosome segregation by SMC complexes and Top2 in S. pombe
    MATTHEW J O'CONNELL; Fiscal Year: 2013
    ..We propose that all three SMC complexes and Top2 functionally interact to guide chromosomes through DNA replication and mitosis...
  50. POSTDOCTORAL TRAINING IN TUMOR BIOLOGY
    Michael L Cleary; Fiscal Year: 2013
    ..faculty and their trainees include: molecular mechanisms of transcriptional regulation;chromosomal DNA replication, repair, and recombination;cell cycle control;cancer stem cells;telomere dynamics;physiological mechanisms in ..
  51. LOCALIZED REVISION OF EPIGENETIC LANDSCAPES INDUCED BY DNA DOUBLE-STRAND BREAKS
    Barry P Sleckman; Fiscal Year: 2012
    ..modification (PTM) of histones regulates many biological processes, including gene transcription, DNA replication, and chromosome segregation...
  52. INTERNATIONAL HERPESVIRUS WORKSHOP
    Jay A Nelson; Fiscal Year: 2013
    ..virus structure, mechanism of virus entry and cell-cell spread, membrane proteins, pathogenesis and latency, DNA replication, vaccination and the immune response, transcriptional control, regulation of gene expression, ..
  53. Genetic Analysis of MSM Protein Function in S. Pombe
    Susan L Forsburg; Fiscal Year: 2012
    Accurate DNA replication and maintenance of genome integrity are essential for cell survival. DNA replication stress has been specifically associated with development of cancer...
  54. The MRAD9 Radioresistance Gene
    Howard B Lieberman; Fiscal Year: 2013
    ..pombe rad9, a gene that promotes gamma-ray resistance, UV-resistance, resistance to the DNA replication inhibitor hydroxyurea, and regulates the associated cell cycle checkpoints...
  55. Mechanisms of ATM activation
    Tanya T Paull; Fiscal Year: 2013
    ..This type of DNA damage occurs during DNA replication, as a result of damage from metabolic intermediates, and after exposure to ionizing radiation and ..
  56. Modulation of histone deacetylase activity by a gammaherpesviral kinase
    Bryan C Mounce; Fiscal Year: 2013
    ..that this modulation facilitates viral infection at several stages, including viral gen expression, DNA replication, and infectious virion production...
  57. MECHANISMS OF HUMAN PAPILLOMAVIRUS DNA REPLICATION
    Louise T Chow; Fiscal Year: 2013
    ..With a thorough understanding of the pathways which HPVs dysregulate and to which HPVs are addicted, targets of therapeutic agents will be identified to serve as the foundation for antiviral drug discovery. ..
  58. INTERACTIONS BETWEEN INTERMEDIATE FILAMENTS AND NUCLEUS
    Robert D Goldman; Fiscal Year: 2013
    ..Nuclear lamins have direct roles in epigenetic regulation of chromatin, DNA replication and repair, transcription, nuclear assembly and disassembly, and in the overall molecular architecture of the ..
  59. FUNCTION AND BIOLOGY OF EUKARYOTIC DNA TOPOISOMERASES
    Neil Osheroff; Fiscal Year: 2013
    ..enzymes that are required for proper chromosome structure and segregation and play important roles in DNA replication, transcription, and recombination...
  60. Telomere extension using nucleoside-modified mRNA and exosomes as a novel therape
    Helen M Blau; Fiscal Year: 2013
    ..at the ends of chromosomes which shorten by about 30-100 bp per year due to oxidation and incomplete DNA replication during S phase of the cell cycle...
  61. Role of ORCA in DNA replication
    Supriya Gangadharan Prasanth; Fiscal Year: 2013
    ..protein complex that serves as the landing pad for the assembly of a multiprotein pre-replicative complex at DNA replication origins...
  62. INTERNATIONAL HERPESVIRUS WORKSHOP
    Jay A Nelson; Fiscal Year: 2010
    ..virus structure, mechanism of virus entry and cell-cell spread, membrane proteins, pathogenesis and latency, DNA replication, vaccination and the immune response, transcriptional control, regulation of gene expression, ..
  63. ANTIMETOBOLITES AND NUCLEAR MATRIX-BOUND DNA REPLICATION
    Daniel Fernandes; Fiscal Year: 1991
    Recent evidence supports the concept that in eucaryotic cells DNA replication are attached to fixed sites on the nuclear matrix, and that template DNA passes through these sites as it is replicated...
  64. HPV DNA REPLICATION: NOVEL HOST FACTORS
    Thomas Melendy; Fiscal Year: 2003
    ..Bruce Stillman studying simian virus 40 (SV40) DNA replication factors and mechanisms. Dr...
  65. Regulation of Mycobacterium tuberculosis proliferation
    Murty Madiraju; Fiscal Year: 2009
    ..Our proposal focuses on DNA replication. interactions with active, but in a non-replicative persistent (NRP) state. growth...
  66. GENETIC STUDIES OF ADENO-ASSOCIATED VIRUS
    Nicholas Muzyczka; Fiscal Year: 1999
    ..One of the unusual aspects of AAV is the mechanism of DNA replication, which involves only leading strand DNA synthesis...
  67. MECHANISMS OF DNA DAMAGE TRIGGERED S PHASE CHECKPOINTS
    Thomas Melendy; Fiscal Year: 2005
    ..of this research is to identify the mechanisms by which the S-phase DNA damage checkpoint responses arrest DNA replication. These checkpoints are the way cells temporarily stop passage through the cell cycle to allow time for repair ..