s phase

Summary

Summary: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.

Top Publications

  1. ncbi Cohesins: chromosomal proteins that prevent premature separation of sister chromatids
    C Michaelis
    Research Institute of Molecular Pathology, Vienna, Austria
    Cell 91:35-45. 1997
  2. ncbi Cancer cell cycles
    C J Sherr
    Howard Hughes Medical Institute, Department of Tumor Cell Biology, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Science 274:1672-7. 1996
  3. 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
  4. pmc A minority of foci or pan-nuclear apoptotic staining of gammaH2AX in the S phase after UV damage contain DNA double-strand breaks
    Sebastien de Feraudy
    Department of Dermatology, University of California, San Francisco, CA 94115, USA
    Proc Natl Acad Sci U S A 107:6870-5. 2010
  5. ncbi A molecular determinant for the establishment of sister chromatid cohesion
    Elcin Unal
    Howard Hughes Medical Institute and Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA
    Science 321:566-9. 2008
  6. 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
  7. 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
  8. 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
  9. pmc Human CtIP promotes DNA end resection
    Alessandro A Sartori
    The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 450:509-14. 2007
  10. 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

Detail Information

Publications366 found, 100 shown here

  1. ncbi Cohesins: chromosomal proteins that prevent premature separation of sister chromatids
    C Michaelis
    Research Institute of Molecular Pathology, Vienna, Austria
    Cell 91:35-45. 1997
    ..A third protein, which we call Scc1p, binds to chromosomes during S phase, dissociates from them at the metaphase-to-anaphase transition, and is degraded by the anaphase promoting complex...
  2. ncbi Cancer cell cycles
    C J Sherr
    Howard Hughes Medical Institute, Department of Tumor Cell Biology, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Science 274:1672-7. 1996
    ..Like the tumor suppressor protein p53, components of this "RB pathway," although not essential for the cell cycle per se, may participate in checkpoint functions that regulate homeostatic tissue renewal throughout life...
  3. 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...
  4. pmc A minority of foci or pan-nuclear apoptotic staining of gammaH2AX in the S phase after UV damage contain DNA double-strand breaks
    Sebastien de Feraudy
    Department of Dermatology, University of California, San Francisco, CA 94115, USA
    Proc Natl Acad Sci U S A 107:6870-5. 2010
    ..mutated kinase and JNK mediated the UV-induced pan-nuclear gammaH2Ax, which preceded and paralleled UV-induced S phase apoptosis...
  5. ncbi A molecular determinant for the establishment of sister chromatid cohesion
    Elcin Unal
    Howard Hughes Medical Institute and Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA
    Science 321:566-9. 2008
    ..Smc3p acetylation is induced in S phase after the chromatin loading of cohesin and is suppressed in G(1) and G(2)/M...
  6. 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
    Replicated chromosomes are held together by the chromosomal cohesin complex from the time of their synthesis in S phase onward...
  7. 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
    ..with some origins firing on average earlier (early-firing origins) and others later (late-firing origins) in the S phase of the budding yeast cell cycle. However, the molecular basis for such temporal regulation is poorly understood.
  8. 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
    ..Recently, Chk1 has also been implicated in regulating different aspects of unperturbed S phase. Using mammalian and avian cells with compromised Chk1 activity, we show that an increase in active replicons ..
  9. pmc Human CtIP promotes DNA end resection
    Alessandro A Sartori
    The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 450:509-14. 2007
    ..These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination...
  10. 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
    ....
  11. pmc H3.3 is deposited at centromeres in S phase as a placeholder for newly assembled CENP-A in G₁ phase
    Elaine M Dunleavy
    Department of Genome Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
    Nucleus 2:146-57. 2011
    ..Centromeric DNA is replicated during S phase; however unlike replication-coupled assembly of canonical histones during S phase, newly synthesized CENP-A ..
  12. ncbi Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast
    Jinglan Zhang
    Center for Molecular Discovery, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Mol Cell 31:143-51. 2008
    Sister chromatid cohesion is normally established in S phase in a process that depends on the cohesion establishment factor Eco1, a conserved acetyltransferase...
  13. ncbi Regulation of replication fork progression through histone supply and demand
    Anja Groth
    Laboratory of Nuclear Dynamics and Genome Plasticity, UMR218 CNRS Institut Curie, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    Science 318:1928-31. 2007
    ....
  14. pmc Cascades of multisite phosphorylation control Sic1 destruction at the onset of S phase
    Mardo Kõivomägi
    Institute of Technology, University of Tartu, Tartu 50411, Estonia
    Nature 480:128-31. 2011
    ..In Saccharomyces cerevisiae, the initiation of S phase is thought to be governed by complexes of Cdk1 and Cln cyclins that phosphorylate six or more sites on the Clb5-..
  15. pmc The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks
    Katsuhiro Hanada
    Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands
    EMBO J 25:4921-32. 2006
    ..endonuclease, is involved in generating the ICL-induced DSBs in mouse embryonic stem (ES) cells in S phase. Given the DNA junction cleavage specificity of Mus81-Eme1 in vitro, DNA damage-stalled replication forks are ..
  16. 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...
  17. 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
    ..Here, we show that chemical or genetic ablation of human Chk1 triggered supraphysiological accumulation of the S phase-promoting Cdc25A phosphatase, prevented ionizing radiation (IR)-induced degradation of Cdc25A, and caused ..
  18. pmc PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex
    Tarek Abbas
    Department of Biochemistry and Molecular Genetics, University of Virginia, School of Medicine, Charlottesville, Virginia 22908, USA
    Genes Dev 22:2496-506. 2008
    ..Finally, we show that the CRL4(Cdt2) and the SCF(Skp2) ubiquitin ligases are redundant with each other in promoting the degradation of p21 during an unperturbed S phase of the cell cycle.
  19. ncbi Cyclin E-CDK2 is a regulator of p27Kip1
    R J Sheaff
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center FHCRC, Seattle, Washington 98104, USA
    Genes Dev 11:1464-78. 1997
    ..phosphorylation of p27 results in elimination of p27 from the cell, allowing cells to transit from G1 to S phase. Moreover, mutation of T187 in p27 to alanine creates a p27 protein that causes a G1 block resistant to cyclin E ..
  20. 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
    ..that a loss of dormant origins results in an increased number of stalled replication forks, even in unchallenged S phase in primary mouse fibroblasts derived from embryos homozygous for the Mcm4(Chaos3) allele...
  21. ncbi Inhibition of notch signaling in human embryonic stem cell-derived neural stem cells delays G1/S phase transition and accelerates neuronal differentiation in vitro and in vivo
    Lodovica Borghese
    Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn and Hertie Foundation, Bonn, Germany
    Stem Cells 28:955-64. 2010
    ..Thus, interference with Notch signaling provides a tool for controlling human NSC differentiation both in vitro and in vivo...
  22. pmc The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition
    Nicole Cloonan
    Institute for Molecular Bioscience, The University of Queensland, Carmody Road, St Lucia, 4072, Australia
    Genome Biol 9:R127. 2008
    ....
  23. 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
    ..Using a cell-free system, we showed that FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. Removal of FANCD2 from extracts inhibits both nucleolytic incisions near the ICL and translesion DNA synthesis ..
  24. pmc Yeast Rtt109 promotes genome stability by acetylating histone H3 on lysine 56
    Robert Driscoll
    Wellcome Trust and Cancer Research U K Gurdon Institute and the Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Science 315:649-52. 2007
    ..These data establish Rtt109p as a member of a new class of histone acetyltransferases and show that its actions are critical for cell survival in the presence of DNA damage during S phase.
  25. pmc Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control
    Srividya Bhaskara
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mol Cell 30:61-72. 2008
    ..Moreover, we noted that Hdac3-/- MEFs were protected from DNA damage when quiescent, which may provide a mechanistic basis for the action of HDAC inhibitors on cycling tumor cells...
  26. 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...
  27. 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
    ..Both branches of this pathway are believed to occur in S phase in order to ensure replication completion...
  28. ncbi GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks
    Agnieszka Gambus
    Cancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK
    Nat Cell Biol 8:358-66. 2006
    ..large replisome progression complexes (RPCs) that are assembled during initiation and disassembled at the end of S phase. RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the ..
  29. ncbi An Smc3 acetylation cycle is essential for establishment of sister chromatid cohesion
    Frederic Beckouët
    Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK
    Mol Cell 39:689-99. 2010
    ..Establishment of cohesion during S phase depends on acetylation of Smc3's nucleotide-binding domain (NBD) by the Eco1 acetyl transferase...
  30. pmc Mouse centric and pericentric satellite repeats form distinct functional heterochromatin
    Mounia Guenatri
    Institut Curie Research section, UMR218 du Centre National pour la Recherche Scientifique, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    J Cell Biol 166:493-505. 2004
    ..Thus, we define functionally independent centromeric subdomains, which spatio-temporal isolation is proposed to be important for centromeric cohesion and dissociation during chromosome segregation...
  31. ncbi CDK activity antagonizes Whi5, an inhibitor of G1/S transcription in yeast
    Michael Costanzo
    Department of Medical Genetics and Microbiology, University of Toronto, 1 King s College Circle, Toronto, M5S 1A8, Canada
    Cell 117:899-913. 2004
    ..Elimination of CDK activity at the end of mitosis allows Whi5 to reenter the nucleus to again repress G1/S transcription. These findings harmonize G1/S control in eukaryotes...
  32. pmc Kinetochore microtubule interaction during S phase in Saccharomyces cerevisiae
    Etsushi Kitamura
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Genes Dev 21:3319-30. 2007
    ..show that centromeres are detached from microtubules for 1-2 min and displaced away from a spindle pole in early S phase. These detachment and displacement events are caused by centromere DNA replication, which results in disassembly ..
  33. pmc Condensin II initiates sister chromatid resolution during S phase
    Takao Ono
    Chromosome Dynamics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351 0198, Japan
    J Cell Biol 200:429-41. 2013
    ..Here, we report that condensin II changes its chromatin-binding property during S phase. Remarkably, advanced premature chromosome condensation (PCC) assays enabled us to visualize condensin II forming ..
  34. 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
    ..Origin firing is also inhibited during the S phase when DNA damage or replication fork stalling activates the checkpoint kinases...
  35. pmc DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity
    Noam Diamant
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Nucleic Acids Res 40:170-80. 2012
    ..replication-blocking lesions, and being associated with chromosomal replication was presumed to occur in the S phase of the cell cycle...
  36. pmc PcG complexes set the stage for epigenetic inheritance of gene silencing in early S phase before replication
    Chiara Lanzuolo
    Epigenetics and Genome Reprogramming, Dulbecco Telethon Institute, IRCCS Santa Lucia Foundation, Rome, Italy
    PLoS Genet 7:e1002370. 2011
    ..Here we identified a specific time window, the early S phase, in which PcG proteins are recruited at BX-C PRE target sites in concomitance with H3K27me3 repressive mark ..
  37. pmc Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells
    J D Singer
    Division of Basic Sciences, Howard Hughes Medical Institute, Seattle, Washington 98109 USA
    Genes Dev 13:2375-87. 1999
    ..ectoderm, in which cells undergo a standard mitotic cycle, there was a greatly increased number of cells in S phase. In the trophectoderm, in which cells go through endocycles, there was a block to entry into S phase...
  38. ncbi H2AX phosphorylation marks gemcitabine-induced stalled replication forks and their collapse upon S-phase checkpoint abrogation
    Brett Ewald
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cancer Ther 6:1239-48. 2007
    ..Thus, H2AX becomes phosphorylated and forms nuclear foci in response to gemcitabine-induced stalled replication forks, and this is greatly increased upon checkpoint abrogation...
  39. ncbi Mitotic kinases as regulators of cell division and its checkpoints
    E A Nigg
    Max Planck Institute for Biochemistry, Department of Cell Biology, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Nat Rev Mol Cell Biol 2:21-32. 2001
    ..Here, I give an overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission...
  40. ncbi Cyclin specificity in the phosphorylation of cyclin-dependent kinase substrates
    Mart Loog
    Department of Physiology, University of California, San Francisco, California 94143 2200, USA
    Nature 434:104-8. 2005
    ..Phosphorylation of Clb5-specific targets during S phase was reduced by replacing Clb5 with Clb2 or by mutating the substrate RXL motif, confirming the importance of Clb5 ..
  41. ncbi ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones
    Rita S Cha
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Science 297:602-6. 2002
    ..Thus, Mec1 has important functions in normal S phase and the genome instability of mec1 (and, analogously, ATR-/-) mutants stems from defects in these basic roles.
  42. pmc DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1
    Jennifer A Cobb
    University of Geneva, Department of Molecular Biology, Quai Ernest Ansermet 30, CH 1211 Geneva, Switzerland
    EMBO J 22:4325-36. 2003
    ..In budding yeast, the intra-S phase checkpoint responds to stalled replication forks by downregulating late-firing origins, preventing spindle ..
  43. pmc The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase
    Kazuki Mochizuki
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892, USA
    J Biol Chem 283:9040-8. 2008
    ..by serum starvation and released, Brd4 knockdown cells were arrested at G(1), whereas control cells progressed to S phase. In microarray analysis, although numerous genes were up-regulated during G(1) in control cells, many of these G(..
  44. ncbi A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1
    Jianping Jin
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 23:709-21. 2006
    ..Cdt2, functions in Xenopus egg extracts and human cells to destroy the replication licensing protein Cdt1 in S phase and after DNA damage. Depletion of human Cdt2 causes rereplication and checkpoint activation...
  45. pmc Replisome instability, fork collapse, and gross chromosomal rearrangements arise synergistically from Mec1 kinase and RecQ helicase mutations
    Jennifer A Cobb
    Frontiers in Genetics NCCR Program, University of Geneva, Switzerland
    Genes Dev 19:3055-69. 2005
    ..Finally, confirming its unique role during replicative stress, Mec1, and not Tel1, is shown to modify fork-associated histone H2A...
  46. 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
    ..We suggest a model in which the distinct timing of DNA replication serves as an epigenetic mechanism for the inheritance of centromere position...
  47. pmc Cdk1-dependent destruction of Eco1 prevents cohesion establishment after S phase
    Nicholas A Lyons
    Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA
    Mol Cell 42:378-89. 2011
    ..Cohesion establishment is restricted to S phase of the cell cycle, but the molecular basis of this regulation is unknown...
  48. 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...
  49. pmc NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells
    Jie Jessie Lin
    Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA
    Cancer Res 70:10310-20. 2010
    ..Cells in S phase were most susceptible, suggesting that MLN4924 will be most toxic on highly proliferating cancers...
  50. ncbi How proteolysis drives the cell cycle
    R W King
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Science 274:1652-9. 1996
    ..Proteolysis therefore drives cell cycle progression not only by regulating CDK activity, but by directly influencing chromosome and spindle dynamics...
  51. ncbi A central role for DNA replication forks in checkpoint activation and response
    José Antonio Tercero
    Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom
    Mol Cell 11:1323-36. 2003
    ..Moreover, recruitment of Ddc2 to nuclear foci and subsequent activation of the Rad53 kinase only occur during S phase and require the assembly of replication forks...
  52. ncbi ATR, Claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage
    Claus Storgaard Sørensen
    Danish Cancer Society, Institute of Cancer Biology, Copenhagen, Denmark
    Cell Cycle 3:941-5. 2004
    ..Here, we show that during physiological S phase the regulation of the Chk1-Cdc25A pathway depends on ATR, Claspin, Rad9, and Hus1...
  53. pmc CRL4(Cdt2)-mediated destruction of the histone methyltransferase Set8 prevents premature chromatin compaction in S phase
    Richard C Centore
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
    Mol Cell 40:22-33. 2010
    ..Set8 levels decline in S phase, but why and how this occurs is unclear...
  54. ncbi Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase
    Gil Bornstein
    Unit of Biochemistry, The B Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa 31096, Israel
    J Biol Chem 278:25752-7. 2003
    ..for an SCF (Skp1-Cullin1-F-box protein) ubiquitin ligase complex, which contains the F-box protein Skp2 (S phase kinase-associated protein 2) and the accessory protein Cks1 (cyclin kinase subunit 1)...
  55. pmc Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases
    David Cortez
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 101:10078-83. 2004
    ..Thus, the MCM complex is a platform for multiple DNA damage-dependent regulatory signals that control DNA replication...
  56. ncbi E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases
    Shweta Tyagi
    Center for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland
    Mol Cell 27:107-19. 2007
    ..by repressing and activating the transcription of genes required for cell-cycle progression, particularly the S phase. E2F proteins repress transcription in association with retinoblastoma pocket proteins, but less is known about ..
  57. pmc A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase
    Kasturi Mitra
    Cell Biology and Metabolism Branch, National Institutes of Health, Building 18T, Room 101, 18 Library Drive, Bethesda, MD 20892 5430, USA
    Proc Natl Acad Sci U S A 106:11960-5. 2009
    ..Depolarizing mitochondria at early G(1) to prevent these changes causes cell cycle progression into S phase to be blocked...
  58. ncbi Checking on DNA damage in S phase
    Jiri Bartek
    Danish Cancer Society, Institute of Cancer Biology, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Nat Rev Mol Cell Biol 5:792-804. 2004
    ....
  59. pmc Characterization of homologous recombination induced by replication inhibition in mammalian cells
    Y Saintigny
    UMR217 CNRS-CEA and CEA, Direction des Sciences du Vivant, , , 92 265 Fontenay aux Roses Cedex, France
    EMBO J 20:3861-70. 2001
    ..We propose that replication inhibition produces DSBs, which are first processed by the NHEJ; then, following DSB accumulation, RAD51 recombination can act...
  60. 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
    ..After helicase loading, we found that the Dbf4-dependent Cdc7 kinase (DDK) but not S phase cyclin-dependent kinase (S-CDK) is required for the initial origin recruitment of Sld3 and the Cdc45 helicase-..
  61. pmc Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate
    Michael J Emanuele
    Division of Genetics, Howard Hughes Medical Institute, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:9845-50. 2011
    ..with proliferating cell nuclear antigen (PCNA), and depletion of PAF15 decreases the number of cells in S phase, suggesting a role for it in cell cycle regulation...
  62. ncbi Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry
    Xiaodong Huang
    Department of Physiological Chemistry, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Mol Cell 42:511-23. 2011
    ..USP37 overexpression caused premature cyclin A accumulation in G1 and accelerated S phase entry, whereas USP37 knockdown delayed these events...
  63. ncbi Hos1 deacetylates Smc3 to close the cohesin acetylation cycle
    Vanessa Borges
    Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, London WC2A 3PX, UK
    Mol Cell 39:677-88. 2010
    ..In budding yeast, cohesin is loaded onto chromosomes during the G1 phase of the cell cycle. During S phase, the replication fork-associated acetyltransferase Eco1 acetylates the cohesin subunit Smc3 to promote the ..
  64. ncbi DNA double-strand breaks associated with replication forks are predominantly repaired by homologous recombination involving an exchange mechanism in mammalian cells
    C Arnaudeau
    Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Stockholm, S-106 91, Sweden
    J Mol Biol 307:1235-45. 2001
    ..We demonstrate that DSB associated with replication forks induce HR at the hprt gene in early S phase. Further analysis revealed that these HR events involve an exchange mechanism...
  65. pmc Mi-2/NuRD complex function is required for normal S phase progression and assembly of pericentric heterochromatin
    Jennifer K Sims
    Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Mol Biol Cell 22:3094-102. 2011
    ..a dampened DNA damage response results in a slow-growth phenotype characterized by delayed progression through S phase. Furthermore, we observe defects in pericentric heterochromatin maintenance and assembly...
  66. ncbi Genome-organizing factors Top2 and Hmo1 prevent chromosome fragility at sites of S phase transcription
    Rodrigo Bermejo
    Fondazione IFOM Istituto FIRC di Oncologia Moleculare IFOM IEO Campus, Via Adamello 16, 20139 Milan, Italy
    Cell 138:870-84. 2009
    ..We have investigated the contribution of Top2 in S phase transcription. Specifically in S phase, Top2 binds intergenic regions close to transcribed genes...
  67. pmc ATR inhibition selectively sensitizes G1 checkpoint-deficient cells to lethal premature chromatin condensation
    P Nghiem
    Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 98:9092-7. 2001
    ..We present a molecular model for how ATR prevents PCC and suggest that ATR represents an attractive therapeutic target for selectively killing cancer cells by premature chromatin condensation...
  68. pmc Cdc7p-Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway
    M Weinreich
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    EMBO J 18:5334-46. 1999
    ..Cdc7p-Dbf4p efficiently phosphorylates several proteins that are required for the initiation of DNA replication, including five of the six Mcm proteins and the p180 subunit of DNA polymerase alpha-primase...
  69. pmc CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation
    Hideo Nishitani
    Graduate School of Life Science, University of Hyogo, Kamigori, Ako gun, Hyogo, 678 1297, Japan
    J Biol Chem 283:29045-52. 2008
    ..The CDK inhibitor p21, another PCNA-binding protein, is also degraded both in S phase and after UV irradiation...
  70. pmc Distinct targets of the Eco1 acetyltransferase modulate cohesion in S phase and in response to DNA damage
    Jill M Heidinger-Pauli
    Howard Hughes Medical Institute, Carnegie Institution, Baltimore, MD 21218, USA
    Mol Cell 34:311-21. 2009
    ..Here we provide insight into how cohesion generation is restricted to S phase but can be activated in G2/M by a DSB in budding yeast. We show that Wpl1p inhibits cohesion in G2/M...
  71. 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
    Origins of replication are activated throughout the S phase of the cell cycle such that some origins fire early and others fire late to ensure that each chromosome is completely replicated in a timely fashion...
  72. ncbi A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor
    Brigitte Goulet
    Department of Biochemistry, McGill University, 687 Pine Avenue West, Montreal H3A 1A1, Canada
    Mol Cell 14:207-19. 2004
    ..Overall, these results uncover an as yet unsuspected role for cysteine proteases in the control of cell cycle progression...
  73. pmc PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells
    G Castoria
    Dipartimento di Patologia Generale, Facolta di Medicina e Chirurgia, II Universita di Napoli, Via L De Crecchio, 7, 80138 Napoli, Italy
    EMBO J 20:6050-9. 2001
    ..The ternary complex probably favours hormone activation of Src- and PI3-kinase-dependent pathways, which converge on cell cycle progression...
  74. ncbi The multiple checkpoint functions of CHK1 and CHK2 in maintenance of genome stability
    Yue Chen
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong
    Front Biosci 13:5016-29. 2008
    ..of the ATM/ATR-CHK1/CHK2-CDC25-CDK axis underlie the molecular basis of the replication checkpoint, the intra-S phase checkpoint, and the G2 DNA damage checkpoint...
  75. ncbi The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase
    H Nishitani
    Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812 8582, Japan
    J Biol Chem 276:44905-11. 2001
    ..These results suggest that the presence of active hCdt1 may be crucial for determining when licensing is legitimate in human cells...
  76. ncbi Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin
    J N Sarkaria
    Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA
    Cancer Res 58:4375-82. 1998
    ..These results identify wortmannin as an inhibitor of ATM activity and suggest that ATM and DNA-PK are relevant targets for the radiosensitizing effect of this drug in cancer cells...
  77. ncbi Multisite phosphorylation and the countdown to S phase
    R J Deshaies
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 107:819-22. 2001
    ..This numerical wizardry suggests how analog inputs can be rectified to digital outputs. Unraveling the counting mechanism promises to generate new insights into the architecture of protein nanoprocessors...
  78. ncbi Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration
    Kin Tak Chan
    Department of Technology and Product Development, CK Life Sciences Int l, Holdings Inc, 2 Dai Fu Street, Tai Po Industrial Estate, Hong Kong SAR, China
    Cancer Lett 294:118-24. 2010
    ..Treatment with cucurbitacin B induced S phase arrest and apoptosis. The growth inhibition effect was associated with cyclin D1 and cdc-2 down regulations...
  79. pmc B-Myb is critical for proper DNA duplication during an unperturbed S phase in mouse embryonic stem cells
    Maëlle Lorvellec
    Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom
    Stem Cells 28:1751-9. 2010
    ..transcriptional regulation of cell cycle proliferation factors, namely c-Myc and FoxM1, which dictate normal S phase progression...
  80. pmc p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage
    H Christian Reinhardt
    Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18 580, Cambridge, MA 02139, USA
    Cancer Cell 11:175-89. 2007
    ..MK2 depletion in p53-deficient cells, but not in p53 wild-type cells, caused abrogation of the Cdc25A-mediated S phase checkpoint after cisplatin exposure and loss of the Cdc25B-mediated G2/M checkpoint following doxorubicin ..
  81. pmc Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase
    Halfdan Beck
    Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen N, Denmark
    J Cell Biol 188:629-38. 2010
    ..Strikingly, WEE1 depletion rapidly induced DNA damage in S phase in newly replicated DNA, which was accompanied by a marked increase in single-stranded DNA...
  82. pmc Acetylation of histone H3 lysine 56 regulates replication-coupled nucleosome assembly
    Qing Li
    Department of Biochemistry and Molecular Biology, Mayo Clinic, College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
    Cell 134:244-55. 2008
    ..These results reveal a mechanism by which H3K56Ac regulates replication-coupled nucleosome assembly mediated by CAF-1 and Rtt106...
  83. pmc Transcriptional activation of histone genes requires NPAT-dependent recruitment of TRRAP-Tip60 complex to histone promoters during the G1/S phase transition
    Michael DeRan
    Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Mol Cell Biol 28:435-47. 2008
    ..Thus, our data support a model in which NPAT recruits the TRRAP-Tip60 complex to histone gene promoters to coordinate the transcriptional activation of multiple histone genes during the G(1)/S-phase transition...
  84. pmc Sld2, which interacts with Dpb11 in Saccharomyces cerevisiae, is required for chromosomal DNA replication
    Y Kamimura
    Department of Biochemistry and Molecular Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565 0871 Japan
    Mol Cell Biol 18:6102-9. 1998
    ..DNA polymerase II (epsilon), one of three replicative DNA polymerases, is required for DNA replication and the S phase checkpoint in Saccharomyces cerevisiae...
  85. pmc The critical mutagenic translesion DNA polymerase Rev1 is highly expressed during G(2)/M phase rather than S phase
    Lauren S Waters
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 103:8971-6. 2006
    ..of Rev1 protein are approximately 50-fold higher in G(2) and throughout mitosis than during G(1) and much of S phase. Differential survival of a rev1Delta strain after UV irradiation at various points in the cell cycle indicates ..
  86. ncbi A role for the transcription factors Mbp1 and Swi4 in progression from G1 to S phase
    C Koch
    Institute of Molecular Pathology, Vienna, Austria
    Science 261:1551-7. 1993
    ..Mbp1 is related to Swi4. Strains deleted for both MBP1 and SWI4 were inviable, demonstrating that transcriptional activation by MBF and SBF has an important role in the transition from G1 to S phase.
  87. ncbi CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast
    Seiji Tanaka
    Division of Microbial Genetics, National Institute of Genetics, Research Organization of Information and Systems, SOKENDAI, Yata 1111, Mishima, Shizuoka 411 8540, Japan
    Nature 445:328-32. 2007
    ..At the onset of S phase, active CDK is essential for chromosomal DNA replication, although its precise role is unknown...
  88. ncbi Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast
    Philip Zegerman
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 445:281-5. 2007
    ..We identified two S phase CDK (S-CDK) phosphorylation sites in the budding yeast Sld3 protein that, together, are essential for DNA ..
  89. pmc Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes
    Judd C Rice
    Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, Virginia 22908 0733, USA
    Genes Dev 16:2225-30. 2002
    ..These data suggest that H4 Lys 20 methylation by PR-Set7 during mitosis acts to antagonize H4 Lys 16 acetylation and to establish a mechanism by which this mark is epigenetically transmitted...
  90. pmc Separate domains of Rev1 mediate two modes of DNA damage bypass in mammalian cells
    Jacob G Jansen
    Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands
    Mol Cell Biol 29:3113-23. 2009
    ..These gaps are inducers of DNA damage signaling leading to an irreversible G(2) arrest. Our results corroborate a model in which Rev1-mediated DNA damage bypass at postreplicative gaps quenches irreversible DNA damage responses...
  91. ncbi Hypoxia inhibits G1/S transition through regulation of p27 expression
    L B Gardner
    Department of Medicine, The Johns Hopkins Oncology Center, Baltimore, Maryland 21205, USA
    J Biol Chem 276:7919-26. 2001
    ..cyclin-dependent kinase inhibitor p27 is induced by hypoxia, thereby inhibiting CDK2 activity and forestalling S phase entry through retinoblastoma protein hypophosphorylation...
  92. ncbi Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53
    Hélène Tourrière
    Institute of Human Genetics, Centre National de la Recherche Scientifique, UPR 1142, 34396 Montpellier Cedex 5, France
    Mol Cell 19:699-706. 2005
    ..The critical role of Mrc1p in HU is therefore to promote fork recovery in a Rad53p-independent manner, presumably through the formation of a stable fork-pausing complex...
  93. pmc SET8 is degraded via PCNA-coupled CRL4(CDT2) ubiquitylation in S phase and after UV irradiation
    Stine Jørgensen
    Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark
    J Cell Biol 192:43-54. 2011
    ..In this study, we show that SET8 is targeted for degradation during S phase by the CRL4(CDT2) ubiquitin ligase in a proliferating cell nuclear antigen (PCNA)-dependent manner...
  94. pmc Regulation of late G1/S phase transition and APC Cdh1 by reactive oxygen species
    Courtney G Havens
    Howard Hughes Medical Institute, Department of Cellular and Molecular Medicine, University of California San Diego, School of Medicine, 9500 Gilman Dr, La Jolla, CA 92093 0686, USA
    Mol Cell Biol 26:4701-11. 2006
    ..and reactive oxygen species (ROS) levels in highly synchronized cell populations progressing from early G1 to S phase. We found that ROS steadily increased, compared to cell size and mitochondrial mass, through the cell cycle...
  95. pmc Chk1 promotes replication fork progression by controlling replication initiation
    Eva Petermann
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom
    Proc Natl Acad Sci U S A 107:16090-5. 2010
    ..Metazoan cells contain many more potential origins than are activated (fired) during each S phase. Origin activation is controlled by the ATR checkpoint kinase and its downstream effector kinase Chk1, which ..
  96. 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...
  97. pmc Pathways of DNA double-strand break repair during the mammalian cell cycle
    Kai Rothkamm
    Fachrichtung Biophysik, Universitat des Saarlandes, D 66421 Homburg Saar, Germany
    Mol Cell Biol 23:5706-15. 2003
    ..These data provide the first evaluation of the cell cycle-specific contributions of NHEJ and HR to the repair of radiation-induced versus replication-associated DSBs...
  98. pmc Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109
    Jeffrey Fillingham
    Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research CCBR, University of Toronto, 160 College St, Toronto, Ontario M5S 3E1, Canada
    Mol Cell Biol 28:4342-53. 2008
    ..Asf1 also physically interacts with the nuclear Hat1/Hat2/Hif1 complex that acetylates H4-K5 and H4-K12. We suggest Asf1 is capable of assembling into chromatin H3-H4 dimers diacetylated on both H4-K5/12 and H3-K9/56...
  99. pmc Increased efficiency of phorbol ester-induced lytic reactivation of Kaposi's sarcoma-associated herpesvirus during S phase
    Shane C McAllister
    Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 NW 185th Ave, Beaverton, OR 97006, USA
    J Virol 79:2626-30. 2005
    ..We report here increased expression of KSHV lytic genes and increased release of progeny virus when synchronized cultures of body cavity-based lymphoma-1 cells are treated with a phorbol ester during S phase of the cell cycle.
  100. pmc Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosis
    J Recht
    Laboratory of Chromatin Biology, The Rockefeller University, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 103:6988-93. 2006
    ..Acetylation of histone H3 lysine 56 (H3 K56ac) in budding yeast occurs during mitotic S phase and persists during DNA damage repair...
  101. ncbi Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains
    Jacob A Aten
    Center for Microscopical Research, Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, P O Box 22700, 1100 DE Amsterdam, Netherlands
    Science 303:92-5. 2004
    ..Our results support the breakage-first theory to explain the origin of chromosomal translocations...

Research Grants72

  1. Prostate cancer chemoprevention by penta-galloyl-glucose
    Junxuan Lu; Fiscal Year: 2013
    ..These multiple targeting activities plus published work supporting anti- angiogenesis activity provide strong rationale for testing the efficacy of PGG for prostate cancer chemoprevention. ..
  2. Inhibition of IkK to treat lethal Graft-vs.-Host Disease
    Patrick Flood; Fiscal Year: 2009
    ..Experiments are proposed in animal models to test the activity of the compound and if successful the long-term goal of this work is to take this compound in human clinical trials for the treatment of GVHD. ..
  3. The Role of MYST Histone Acetyltransferase in Genome Stability
    M Mitchell Smith; Fiscal Year: 2013
    ..We will characterize DNA replication licensing, S phase progression, DNA damage response, and protein occupancy at DNA replication origins to define the involvement of ..
  4. New drug Vida-5 for treating chronic kidney disease progression
    Jinshyun Ruth Wu-Wong; Fiscal Year: 2011
    ..PUBLIC HEALTH RELEVANCE: Vidasym's phase I SBIR study will determine the feasibility of using Vida-5 to treat chronic kidney disease (CKD) progression...
  5. Novel drug VS-105 for treatment of diabetic nephropathy
    Jinshyun Ruth Wu-Wong; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Vidasym's phase I STTR study will investigate the feasibility of using VS-105 to treat chronic kidney disease (CKD) related to ..
  6. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2012
    ..Cell cycle progression is a coordinately regulated process that includes accurate replication of DNA during the S phase, correct segregation of chromosomes during mitosis (M phase) and final separation of daughter cells in ..
  7. Inactivation of Hdac3 in the cause, prevention, and treatment of HCC
    Scott W Hiebert; Fiscal Year: 2013
    ..By contrast, careful analysis of the cell cycle indicated that apoptosis required S phase progression and that S phase was slowed...
  8. Metnase, PIKK, and RPA Roles in DNA Damage and Replication Stress Responses
    Jac A Nickoloff; Fiscal Year: 2013
    ..Cells are particularly vulnerable to DNA damage during S phase because most DNA lesions stall replication forks, causing replication stress...
  9. Roles of the mammalian CST complex in DNA replication and chromosome cohesion
    JASON AARON STEWART; Fiscal Year: 2013
    ..The completion of these studies will advance our understanding of these cellular processes and provide new targets for prevention and treatment of these diseases. ..
  10. The Role of hPso4 in DNA Repair and Chemotherapy Resistance
    Montaser Shaheen; Fiscal Year: 2013
    ..We will deplete this E2 and evaluate if this will achieve the same chemosensitivity as depleting hPso4. This will open the opportunity to identify Ubc3 small molecule inhibitors as cancer therapy. ..
  11. Cyclin-Dependent Kinase Inhibition During S Phase
    Geoffrey I Shapiro; Fiscal Year: 2013
    ..Preliminary data indicate that cdk1 participates in BRCA1-dependent S phase checkpoint control following DNA damage...
  12. Circadian Clock Regulation in Skin
    Bogi Andersen; Fiscal Year: 2013
    ..The work is innovative because it suggests a new role for the circadian clock in imposing temporal separation of metabolism and DNA synthesis in epidermal progenitors. ..
  13. Checkpoints and double strand breaks in S. pombe meiosis
    Susan L Forsburg; Fiscal Year: 2013
    ..However, there has been little investigation of how "normal" checkpoints function in meiotic S phase (meiS) in response to replication stress...
  14. CSHL Eukaryotic DNA Replication Conference
    David J Stewart; Fiscal Year: 2013
    ..Since DNA replication is crucial to cell division, uncontrolled growth is a hallmark of tumors, S phase is a major target for chemo- and radiotherapy and errors in DNA replication lead to genomic instability, the ..
  15. IKKbeta:Bi-Functional Regulator of Hepatocyte Proliferation
    Hyam L Leffert; Fiscal Year: 2010
    ..Attenuated co-regulated expression of hepatocyte IKK[unreadable] and JNK2 may both facilitate hepatocyte proliferation and increase the susceptibility of hepatocytes to carcinogenesis. ..
  16. ATF2 in DNA damage response.
    ZE apos EV A RONAI; Fiscal Year: 2010
    ..Overall, using the powerful genetics of S. Pombe, the relevant mammalian cell cultures combined with genetic mouse models our proposal will provide important new understanding of ATF2 in transcription and DNA damage response. ..
  17. C/EBP beta SIGNALS HEPATOCYTE PROLIFERATION AND SURVIVAL
    Mario Chojkier; Fiscal Year: 2012
    ..We have established that C/EBP(3 affects the GI/S phase transition of the cell cycle...
  18. Cyclin E Regulation in Normal and Neoplastic Hematopoiesis
    ALEXANDER C MINELLA; Fiscal Year: 2013
    ..The investigators now propose to study how high cyclin E levels cause these blood cell defects and contribute to bone marrow failure and cancers. ..
  19. Contribution of Sperm Nucleus to Paternal DNA Replication
    WILLIAM S WARD; Fiscal Year: 2013
    ..This application proposes to test the idea that the sperm cell brings to the egg more than only the DNA, itself, but instructions on how to replicate it properly in the first embryonic cell division. ..
  20. Development of Novel Agents Targeting Genome Stability and Maintenance for Treati
    John J Turchi; Fiscal Year: 2013
    ..Successful completion of these studies will support a phase II STTR application to pursue Investigational New Drug (IND)-enabling studies, including expanded safety, toxicity, and efficacy studies. ..
  21. Regulation and Role of Ornithine Decarboxylase in Cell Proliferation and Cancer
    John L Cleveland; Fiscal Year: 2013
    ..abstract_text> ..
  22. Physiologic Regulation of Hematopoiesis by Notch
    Nadia Carlesso; Fiscal Year: 2011
    ..The long term goal of this project is to evaluate the role of the Notch signaling pathway both in normal bone marrow reconstitution and in leukemias and to identify novel targets of therapeutic intervention. ..
  23. Validation and Development of WEE1 as a therapeutic target in AML
    Christopher C Porter; Fiscal Year: 2013
    ..cell lines and found that the effect of inhibiting Wee1 in combination with cytarabine involves abrogation of the S phase checkpoint induced by cytarabine...
  24. Establishment of sister chromatid cohesion
    Douglas E Koshland; Fiscal Year: 2013
    ..holds together the two sister chromatids (the newly replicated chromosomes) from the time of their synthesis in S phase through metaphase of mitosis...
  25. Functional analysis of Chk2 in DNA damage response
    Jun Hyun Kim; Fiscal Year: 2013
    ..Extensive analyses of Chk2 and Rad53 (yeast Chk2 ortholog) have highlighted the important roles of Chk2 in S phase. Rad53 regulates DNA replication through its functions in transcription, inhibition of origin firing and ..
  26. Control of the Erythroid Terminal Differentiation Decision
    Arthur I Skoultchi; Fiscal Year: 2013
    ..1. The other factors are E2F2 and E2F4, transcriptions factors that play major roles in G1 to S phase cell cycle progression...
  27. Induction of DNA Damage Signaling Cascade upon RVFV Infection
    Kylene Kehn-Hall; Fiscal Year: 2013
    ..These phosphorylation events were also dependent on NSs. In addition, NSs dependent S phase arrest was observed following RVFV infection, which can be reversed by treatment with ATM and Chk.2 inhibitors...
  28. HYPOXIA AND GENE REPRESSION
    Amato J Giaccia; Fiscal Year: 2013
    ..By identifying and characterizing the genes repressed by p53 and HIF through JARID1B during hypoxia, our studies should clarify some of the complex regulatory mechanisms activated in the hypoxic microenvironment. ..
  29. MECHANISMS OF HUMAN PAPILLOMAVIRUS DNA REPLICATION
    Louise T Chow; Fiscal Year: 2013
    ..p130 (a member of the pRB family of pocket proteins) in the differentiated keratinocytes, enabling the S phase reentry and progression necessary for viral DNA amplification...
  30. Replication licensing and cell cycle checkpoints
    Jeanette Gowen Cook; Fiscal Year: 2013
    ..initiation is stimulated by the activity of cyclin dependent protein kinases (Cdks) that are activated at the G1/S phase transition and remain active until mitosis...
  31. FANCD2 interaction with mismatch repair proteins and MCM2-7
    Gary M Kupfer; Fiscal Year: 2013
    ..interaction regulates the assembly of the replication complex at the origin by responding to DNA damage during S phase. Our data indicate that binding to a subset of the MCM subunits results in inhibition of replication complex ..
  32. Telomere extension using nucleoside-modified mRNA and exosomes as a novel therape
    Helen M Blau; Fiscal Year: 2013
    ..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...
  33. Role of Cyclins in Brain Construction and Interneuron Genesis
    KRISTIN GIAMANCO; Fiscal Year: 2013
    ..These studies will contribute to the ultimate goal to devise more effective therapies for neuropsychiatric disorders. ..
  34. Investigating the role of the cell cycle protein E2F1 in HIV-induced neurotoxicit
    Jacob Zyskind; Fiscal Year: 2013
    ..of the transcription factor E2F1, which is known to activate transcription of genes necessary for G1 to S phase progression of the cell cycle...
  35. MOUSE MODELS TO STUDY GONADAL TUMOR DEVELOPMENT
    Martin M Matzuk; Fiscal Year: 2010
    ..is that the inhibin/activin/BMP, RB/E2F, FSH, LH, and cell cycle pathways converge to regulate the G1 to S phase transition and that modulation of the activity (phosphorylation) state of RB by cell cycle regulators (e.g...
  36. New drug VS-501 for treating hyperphosphatemia in chronic kidney disease
    Jinshyun Ruth Wu-Wong; Fiscal Year: 2012
    ..2 billion. PUBLIC HEALTH RELEVANCE: Vidasym's phase I SBIR study will investigate the feasibility of using Vida-501, Vidasym's novel phosphate binder, to treat ..
  37. Inhibition of Reflux-Induced Esophageal Adenocarcinoma by Proanthocyanidins
    Laura A Kresty; Fiscal Year: 2013
    ....
  38. Pathway Choice of DNA Double-Strand Break Repair
    David J Chen; Fiscal Year: 2013
    ..propose the following specific aims: 1) To test the hypothesis that Ku70/80 is required for DNA end stability in S phase of the cell cycle...
  39. Homeostatic Regulation of Folate Metabolism
    Patrick J Stover; Fiscal Year: 2010
    ..Recently, we discovered that cSHMT localizes to the nucleus during the S phase of the cell cycle and that it modified by SUMO...
  40. CHARACTERIZATION OF TUMOR SUPPRESSION BY THE APC GENE
    JOANNA LOUISE GRODEN; Fiscal Year: 2010
    ..Our long-term goals are to elucidate the mechanisms and pathways through which APC functions and, by doing so, to contribute to the design of better therapeutic strategies in oncology. ..
  41. Linking DNA Replication Origin Licensing with Cell Cycle Progression
    Kate E Coleman; Fiscal Year: 2013
    ..Origins are rendered competent, or licensed, for DNA replication in S phase by the chromatin-loading of a DNA helicase known as the Mini-Chromosome Maintenance Complex (MCM) during G1 phase ..
  42. The Role of the DNA Unwinding Element Binding Protein, DUE-B, in DNA Replication
    Michael Leffak; Fiscal Year: 2010
    ..DUE-B is necessary for normal entry into the DNA synthetic S phase of the cell cycle and for the initiation of replication...
  43. The Role of Zinc Finger Genes in Leukemogenesis
    Sinisa Dovat; Fiscal Year: 2013
    ..1) Ikaros is phosphorylated at multiple evolutionarily conserved sites by CK2 and other kinases during G1 and S phase of the cell cycle 2) Phosphorylation of Ikaros at specific amino acids regulates its DNA-binding ability and ..
  44. Effect of anti-S phase agents on human chromosomes
    Anindya Dutta; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Anti-S phase agents like doxorubicin, gemcitabine, cytarabine and hydroxyurea are in extensive use for the treatment of cancers and of hematological diseases such as essential thrombocytopenia, ..
  45. Regulation of Borealin Function by Mitotic Phosphorylation
    William Taylor; Fiscal Year: 2009
    ..Increased proliferation of fibroblasts and smooth muscle cells has also been implicated in diseases of the cardiovascular system, and knowing how Borealin is regulated may also provide insight into this spectrum of diseases. ..
  46. REGULATION OF TRYPANOSOME DNA REPLICATION
    DAN RAY; Fiscal Year: 2009
    ..abstract_text> ..
  47. Plerixafor/G-CSF with Sorafenib for Acute Myelogenous Leukemia with FLT3-ITD Muta
    MICHAEL W ANDREEFF; Fiscal Year: 2012
    ..This effect was not consistent with other inhibitors. In the applicant's Phase 1 study, Sorafenib alone eradicated leukemic cells from circulation and showed a 55% reduction of bone marrow ..
  48. A Novel Carcinogen-Induced Cell Cycle Checkpoint
    Cyrus Vaziri; Fiscal Year: 2013
    ..g. Rad18 or its activating kinases) whose inhibition enhances the efficacy of existing cancer therapies. ..
  49. L2DTL Function in Maintaining Genomic Stability during Drosophila Development
    CATHERINE SILVER KEY; Fiscal Year: 2010
    ..proper expression and timely destruction are an important part of the "once and only" replication control during S phase. Significantly, elevated levels of Cdt1/Dup and its inhibitor Geminin are associated with an increasing number of ..
  50. Identification and characterization of novel epigenetic marks of non-histone prot
    Xiaodong Cheng; Fiscal Year: 2010
    ..abstract_text> ..
  51. Regulation of smooth muscle cell function by CD44 in cardiovascular disease
    ELLEN PURE apos PURE'; Fiscal Year: 2012
    ..In vitro, the native high molecular weight form of HA (HMW-HA) antagonizes mitogen-induced S phase entry of VSMCs while the lower molecular weight forms of HA (LMW- HA) that accumulate at sites of inflammation ..
  52. Mechanistic regulation of tumor specific forms of cyclin E in breast cancer
    NIKKI A DELK; Fiscal Year: 2010
    ..Cyclin E, a cell cycle protein that mediates GO release and G1 to S phase transition, shows a unique tumor-specific deregulation associated with malignancy in breast, ovarian, and ..
  53. Cyclin D1 and vitamin D signaling in oral keratinocyte pathophysiology
    Sanjay M Mallya; Fiscal Year: 2013
    ..The cyclin D1 oncogene plays an important role in OSCC development. Cyclin D1 is a key regulator of the G1-S phase of the cell cycle...
  54. Cyclin A Function in Stem Cells and in Neoplasia
    Peter Sicinski; Fiscal Year: 2013
    ..Specific Aim 2. To determine the molecular function of cyclin A-Cdk1 in stem cells. Specific Aim 3. To test the requirement for cyclin A function in Myc-driven breast cancers. ..
  55. SV40 T Antigen Role in Virus Growth and Transformation
    James M Pipas; Fiscal Year: 2010
    ..T antigen drives cells into S phase by inhibiting the Rb-family of tumor suppressor proteins, and thus activating the expression of genes regulated ..
  56. Germline KLLN Alterations in PTEN Mutation Negative Cowden Syndrome
    EMILY ALISON NIZIALEK; Fiscal Year: 2013
    ....
  57. EUKARYOTIC CHROMOSOME REPLICATION
    Bonita J Brewer; Fiscal Year: 2013
    ..Origins show variation in timing-not all origins fire at the same time in S phase-and in efficiency-not all origins necessarily firing in every cell cycle...
  58. Understanding the Role of Histone Demethylases and Heterochromatin in Cell Cycle
    Johnathan R Whetstine; Fiscal Year: 2013
    ..tri-demethylase as a regulator of chromatin accessibility, heterochromatin (HP13), DNA replication timing and S phase progression...
  59. Pathophysiology and Gene Replacement Strategies for Arginase Deficiency
    Gerald S Lipshutz; Fiscal Year: 2013
    ..viral vectors;3) demonstrated that knockout mouse neurons have a higher percentage of cells in the S phase of the cell cycle;4) shown that differentiated neurons from knockout mice have a more mature morphology;and 5) ..
  60. Mechanism controlling centrosome duplication
    Barbara E Tanos; Fiscal Year: 2013
    ..which cycles between the "engaged" state, where the two centrioles grow orthogonally to one another during S phase, and the "disengaged" state during late mitosis or early G1, where centrioles are no longer tightly opposed...
  61. Role of PALB2 in the DNA damage response and breast cancer suppression
    Bing Xia; Fiscal Year: 2013
    ..g. HR, S phase DNA damage check point, and interstrand crosslink (ICL) repair...
  62. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2012
    ..Such basic understanding of interaction interfaces in repair complexes could be exploited in developing therapeutic intervention strategies for sensitizing tumor cells or protecting healthy cells during chemo/radiation therapy. ..
  63. TRANSCRIPTIONAL CONTROL OF MAMMALIAN BRAIN DEVELOPMENT
    Eseng Lai; Fiscal Year: 2001
    ..where BF-1 expression is under control of tetracycline withdrawal, that the presence of BF-1 promotes entry into S phase in the presence of TGF-b...
  64. CELLULAR EFFECTS OF INHIBITION OF THYMIDYLATE SYNTHASE
    RICHARD MORAN; Fiscal Year: 1993
    ..Finally, an explanation for the limited increase in the host toxicity of 5-FU when folinic acid is simultaneously administered will be sought on a biochemical level...
  65. REGULATION OF P53 IN CERVICAL CARCINOMA BY HEAT/HYPOXIA
    Amato Giaccia; Fiscal Year: 1999
    ....
  66. C-MYC EXPRESSION AND APOPTOSIS IN B CELLS
    GAIL SONENSHEIN; Fiscal Year: 2007
    ..with antisera against their expressed surface IgM (anti- IgM), which serves as B Cell Receptor (BCR), induces G1/S phase growth arrest followed by apoptosis...
  67. Regulation of histone genes upon replication arrest and DNA damage
    HYERYUN PAIK; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  68. MECHANISMS OF CELL CYCLE CONTROL DURING MAMMARY GLAND DE
    Hui Zhang; Fiscal Year: 2001
    ..These studies should also provide a basis to design novel strategies for diagnosis, prognosis, and therapeutic treatment of breast cancers. ..
  69. RAPID ESTIMATION OF HUMAN BRAIN TUMOR GROWTH KINETICS
    Richard Davis; Fiscal Year: 1993
    ..Ll) obtained from tumors that were exposed to a pulse of BUdR at the time of craniotomy have revealed that: 1) S phase fraction (or BUdR Ll) of individual brain tumors measured by BUdR labeling reflect proliferative activity or ..
  70. RADIATION INDUCED CHROMATIN CHANGES IN A DEFINED ORIGIN
    James Larner; Fiscal Year: 2001
    ..A p53-mediated pathway arrests cells in late G1, to temporarily prevent entry into S phase or to shunt them toward apoptosis. A second pathway prevents G cells from undergoing mitosis...
  71. ATM and ATR in Chromium-Induced S-Phase Arrest
    Bo Xu; Fiscal Year: 2005
    ....
  72. MECHANISMS OF DNA DAMAGE TRIGGERED S PHASE CHECKPOINTS
    Thomas Melendy; Fiscal Year: 2005
    ..DNA replication system, which is supported predominantly by human cell extracts, to biochemically investigate S phase DNA damage dependent checkpoints...