proliferating cell nuclear antigen

Summary

Summary: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.

Top Publications

  1. 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
  2. ncbi Principles of ubiquitin and SUMO modifications in DNA repair
    Steven Bergink
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Nature 458:461-7. 2009
  3. 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
  4. pmc Inhibition of homologous recombination by the PCNA-interacting protein PARI
    George Lucian Moldovan
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Mol Cell 45:75-86. 2012
  5. ncbi The multifaceted mismatch-repair system
    Josef Jiricny
    Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Nat Rev Mol Cell Biol 7:335-46. 2006
  6. 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
  7. ncbi The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol η in response to oxidative DNA damage in human cells
    Anastasia Zlatanou
    Group TLS Polymerases and Cancer, Universite Paris Sud, CNRS UMR8200, Institut Gustave Roussy, 94800 Villejuif, France
    Mol Cell 43:649-62. 2011
  8. pmc Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response
    Richard C Centore
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
    Mol Cell 46:625-35. 2012
  9. pmc Regulation of the Fanconi anemia pathway by a SUMO-like delivery network
    Kailin Yang
    Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Genes Dev 25:1847-58. 2011
  10. 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

Research Grants

Detail Information

Publications317 found, 100 shown here

  1. 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
    ..We therefore propose that ZRANB3 maintains genomic stability at stalled or collapsed replication forks by facilitating fork restart and limiting inappropriate recombination that could occur during template switching events...
  2. ncbi Principles of ubiquitin and SUMO modifications in DNA repair
    Steven Bergink
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Nature 458:461-7. 2009
    ....
  3. 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
    PCNA (proliferating cell nuclear antigen) has been found in the nuclei of yeast, plant and animal cells that undergo cell division, suggesting a function in cell cycle regulation and/or DNA replication...
  4. pmc Inhibition of homologous recombination by the PCNA-interacting protein PARI
    George Lucian Moldovan
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Mol Cell 45:75-86. 2012
    ..Thus, we propose that PARI is a long sought-after factor that suppresses inappropriate recombination events at mammalian replication forks...
  5. ncbi The multifaceted mismatch-repair system
    Josef Jiricny
    Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Nat Rev Mol Cell Biol 7:335-46. 2006
    ..This article reviews our current understanding of this multifaceted DNA-repair system in human cells...
  6. 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
    ..b>Proliferating cell nuclear antigen (PCNA)-a cofactor of DNA polymerases that encircles DNA-orchestrates several of these functions by ..
  7. ncbi The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol η in response to oxidative DNA damage in human cells
    Anastasia Zlatanou
    Group TLS Polymerases and Cancer, Universite Paris Sud, CNRS UMR8200, Institut Gustave Roussy, 94800 Villejuif, France
    Mol Cell 43:649-62. 2011
    ....
  8. pmc Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response
    Richard C Centore
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
    Mol Cell 46:625-35. 2012
    ..Thus, as a "reader" of ubiquitylated PCNA, Spartan promotes an unexpected feed-forward loop to enhance PCNA ubiquitylation and translesion DNA synthesis...
  9. pmc Regulation of the Fanconi anemia pathway by a SUMO-like delivery network
    Kailin Yang
    Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Genes Dev 25:1847-58. 2011
    ..We propose that the regulated targeting of USP1/UAF1 to its DNA repair substrates, FANCD2-Ub and PCNA-Ub, by SLD-SIM interactions coordinates homologous recombination and translesion DNA synthesis...
  10. 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
    ..Upon DNA damage, ubiquitination of proliferating cell nuclear antigen (PCNA) induces bypass of the lesion by directing the replication machinery into the TLS pathway...
  11. ncbi Proliferating cell nuclear antigen (PCNA): a dancer with many partners
    Giovanni Maga
    DNA Enzymology and Molecular Virology, Istituto di Genetica Molecolare, IGM CNR, National Research Council, via Abbiategrasso 207, I 27100 Pavia, Italy
    J Cell Sci 116:3051-60. 2003
    b>Proliferating cell nuclear antigen (PCNA) was originally characterised as a DNA sliding clamp for replicative DNA polymerases and as an essential component of the eukaryotic chromosomal DNA replisome...
  12. pmc PARP inhibition versus PARP-1 silencing: different outcomes in terms of single-strand break repair and radiation susceptibility
    Camille Godon
    Institut Curie, Centre de Recherche INSERM, U612, Institut Curie, Bât 110 112, Centre Universitaire, F 91405 Orsay, France
    Nucleic Acids Res 36:4454-64. 2008
    ..PARP-1 inhibition and deletion thus have different outcomes in terms of SSBR and radiosensitivity...
  13. pmc Role of SUMO modification of human PCNA at stalled replication fork
    Himabindu Gali
    Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary
    Nucleic Acids Res 40:6049-59. 2012
    ..Whereas ubiquitylation of proliferating cell nuclear antigen (PCNA) facilitates damage bypass, modification of yeast PCNA by small ubiquitin-like modifier (SUMO) ..
  14. pmc Characterization of human Spartan/C1orf124, an ubiquitin-PCNA interacting regulator of DNA damage tolerance
    Szilvia Juhasz
    Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged 6726, Hungary
    Nucleic Acids Res 40:10795-808. 2012
    ..Replication through DNA lesions depends on mono- and polyubiquitylation of proliferating cell nuclear antigen (PCNA), which enable translesion synthesis (TLS) and template switching, respectively...
  15. ncbi DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage
    Emily J Davis
    Medical Research Council Protein Phosphorylation Unit, Sir James Black Centre, University of Dundee, Dundee, Scotland, UK
    Nat Struct Mol Biol 19:1093-100. 2012
    ..We introduce DVC1 as a regulator of cellular responses to DNA damage that prevents mutations when DNA damage occurs...
  16. pmc Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination
    Kenji Watanabe
    Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
    EMBO J 23:3886-96. 2004
    ..irradiation induces relocalization of Rad18 in the nucleus, thereby stimulating colocalization with proliferating cell nuclear antigen (PCNA), and Rad18/Rad6-dependent PCNA monoubiquitination...
  17. 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
    ..Our findings provide insights into how type 2 RNase H activity is directed during genome replication and repair, and suggest a mechanism by which RNase H2 may suppress generation of immunostimulatory nucleic acids...
  18. ncbi RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO
    Carsten Hoege
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18a, 82152 Martinsried, Germany
    Nature 419:135-41. 2002
    ..ubiquitin-related modifier (SUMO)-conjugating enzyme, is also affiliated with this pathway and that proliferating cell nuclear antigen (PCNA) -- a DNA-polymerase sliding clamp involved in DNA synthesis and repair -- is a substrate...
  19. 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
    The DNA polymerase delta processivity factor Proliferating Cell Nuclear Antigen (PCNA) promotes the DNA damage-induced degradation of the replication initiation factor Cdt1 via the CRL4(Cdt2) E3 ubiquitin ligase complex...
  20. 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
    ..Our approach has revealed the distribution of PRR tracts in a synchronized cell population. It will allow an in-depth mechanistic analysis of how cells manage the processing of lesions to their genomes during and after replication...
  21. ncbi 8-oxo-guanine bypass by human DNA polymerases in the presence of auxiliary proteins
    Giovanni Maga
    Institute of Molecular Genetics IGM CNR, via Abbiategrasso 207, I 27100 Pavia, Italy
    Nature 447:606-8. 2007
    ..Here we analyse the effects of human proliferating cell nuclear antigen (PCNA) and replication protein A (RP-A) on six different human DNA pols--belonging to the B, Y and X ..
  22. 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...
  23. ncbi Endonucleolytic function of MutLalpha in human mismatch repair
    Farid A Kadyrov
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Cell 126:297-308. 2006
    ..Therefore, the mode of excision initiation may differ in these organisms...
  24. pmc ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin
    Kyoo Young Lee
    Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 200:31-44. 2013
    ..Reduced expression of ATAD5 extended the lifespan of replication factories by retaining proliferating cell nuclear antigen (PCNA) and other replisome proteins on the chromatin during and even after DNA synthesis...
  25. ncbi DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks
    Anna Mosbech
    Ubiquitin Signaling Group, Department of Disease Biology, Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Nat Struct Mol Biol 19:1084-92. 2012
    ..Our findings establish DVC1 as a DNA damage-targeting p97 adaptor that protects cells from deleterious consequences of replication blocks and suggest an important role of p97 in ubiquitin-dependent regulation of TLS...
  26. pmc SHPRH and HLTF act in a damage-specific manner to coordinate different forms of postreplication repair and prevent mutagenesis
    Jia Ren Lin
    Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA
    Mol Cell 42:237-49. 2011
    ....
  27. pmc PCNA is required for initiation of recombination-associated DNA synthesis by DNA polymerase delta
    Xuan Li
    Department of Microbiology, University of California, Davis, 95616 8665, USA
    Mol Cell 36:704-13. 2009
    ..We conclude that PCNA has a specific role in the initiation of recombination-associated DNA synthesis and that DNA polymerase delta promotes recombination-associated DNA synthesis...
  28. ncbi Regulation of monoubiquitinated PCNA by DUB autocleavage
    Tony T Huang
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Nat Cell Biol 8:339-47. 2006
    ..Our results define a regulatory mechanism for protein ubiquitination that involves the signal-induced degradation of an inhibitory DUB...
  29. ncbi The replication clamp-loading machine at work in the three domains of life
    Chiara Indiani
    Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10021, USA
    Nat Rev Mol Cell Biol 7:751-61. 2006
    ..Moreover, these studies highlight the evolutionary conservation of the clamp-loading process in the three domains of life...
  30. ncbi The Elg1 replication factor C-like complex functions in PCNA unloading during DNA replication
    Takashi Kubota
    Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK
    Mol Cell 50:273-80. 2013
    ....
  31. pmc Structural basis for recruitment of human flap endonuclease 1 to PCNA
    Shigeru Sakurai
    Structural Biology Laboratory, Nara Institute of Science and Technology, Takayama, Ikoma, Nara, Japan
    EMBO J 24:683-93. 2005
    Flap endonuclease-1 (FEN1) is a key enzyme for maintaining genomic stability and replication. Proliferating cell nuclear antigen (PCNA) binds FEN1 and stimulates its endonuclease activity...
  32. ncbi The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA
    Jafar Sharif
    Tohoku University Biomedical Engineering Research Organization TUBERO, 2 1 Seiryo machi, Aoba ku, Sendai 980 8575, Japan
    Nature 450:908-12. 2007
    ..The link between hemi-methylated DNA, Np95 and Dnmt1 thus establishes key steps of the mechanism for epigenetic inheritance of DNA methylation...
  33. ncbi Multiple roles of the cell cycle inhibitor p21(CDKN1A) in the DNA damage response
    Ornella Cazzalini
    Dipartimento di Medicina Sperimentale, sez Patologia generale C Golgi, Universita di Pavia, 27100 Pavia, Italy
    Mutat Res 704:12-20. 2010
    ..and DNA translesion synthesis (TLS), has been suggested to occur thanks to its interaction with proliferating cell nuclear antigen (PCNA), a crucial protein involved in several aspects of DNA metabolism, and cell-cycle regulation...
  34. ncbi Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin
    K Shibahara
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 96:575-85. 1999
    ..The proliferating cell nuclear antigen (PCNA), a DNA polymerase clamp, is a component of the replication-dependent marking of DNA for ..
  35. pmc Identification of a novel, widespread, and functionally important PCNA-binding motif
    Karin M Gilljam
    Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
    J Cell Biol 186:645-54. 2009
    Numerous proteins, many essential for the DNA replication machinery, interact with proliferating cell nuclear antigen (PCNA) through the PCNA-interacting peptide (PIP) sequence called the PIP box...
  36. ncbi SUMOylation regulates Rad18-mediated template switch
    Dana Branzei
    IFOM, the FIRC Institute for Molecular Oncology Foundation, IFOM IEO Campus, Via Adamello 16, 20139 Milan, Italy
    Nature 456:915-20. 2008
    ..Gap-filling repair requires homologous recombination as well as Rad18- and Rad5-mediated proliferating cell nuclear antigen (PCNA) polyubiquitylation...
  37. ncbi Three-dimensional structure of the beta subunit of E. coli DNA polymerase III holoenzyme: a sliding DNA clamp
    X P Kong
    Laboratory of Molecular Biophysics, Rockefeller University, New York, New York 10021
    Cell 69:425-37. 1992
    ..A potential structural relationship is suggested between the beta subunit and proliferating cell nuclear antigen (PCNA, the eukaryotic polymerase delta [and epsilon] processivity factor), and the gene 45 protein ..
  38. ncbi Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA
    J M Gulbis
    Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA
    Cell 87:297-306. 1996
    The crystal structure of the human DNA polymerase delta processivity factor PCNA (proliferating cell nuclear antigen) complexed with a 22 residue peptide derived from the C-terminus of the cell-cycle checkpoint protein p21(WAF1/CIP1) has ..
  39. pmc SUMO modification of PCNA is controlled by DNA
    Joanne L Parker
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, UK
    EMBO J 27:2422-31. 2008
    ..Instead, the stimulatory effect of DNA on conjugation is mainly attributable to DNA binding of PCNA itself. These findings imply a change in the properties of PCNA upon loading that enhances its capacity to be sumoylated...
  40. pmc Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein a
    Adelina A Davies
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK
    Mol Cell 29:625-36. 2008
    ..Association of the ligase with chromatin is detected where RPA is most abundant, and purified RPA can recruit Rad18 to ssDNA in vitro. Our results therefore implicate the RPA complex in the activation of DNA damage tolerance...
  41. pmc Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44
    Benyamin Rosental
    Shraga Segal Department of Microbiology and Immunology, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
    J Immunol 187:5693-702. 2011
    ..We demonstrate that PCNA promotes cancer survival by immune evasion through inhibition of NKp44-mediated NK cell attack...
  42. pmc Repair complexes of FEN1 endonuclease, DNA, and Rad9-Hus1-Rad1 are distinguished from their PCNA counterparts by functionally important stability
    Jordi Querol-Audi
    Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 109:8528-33. 2012
    Processivity clamps such as proliferating cell nuclear antigen (PCNA) and the checkpoint sliding clamp Rad9/Rad1/Hus1 (9-1-1) act as versatile scaffolds in the coordinated recruitment of proteins involved in DNA replication, cell-cycle ..
  43. pmc Small-molecule targeting of proliferating cell nuclear antigen chromatin association inhibits tumor cell growth
    Zongqing Tan
    Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    Mol Pharmacol 81:811-9. 2012
    b>Proliferating cell nuclear antigen (PCNA), a potential anticancer target, forms a homotrimer and is required for DNA replication and numerous other cellular processes...
  44. pmc Identification of small molecule proliferating cell nuclear antigen (PCNA) inhibitor that disrupts interactions with PIP-box proteins and inhibits DNA replication
    Chandanamali Punchihewa
    Department of Chemical Biology and Therapeutics, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 287:14289-300. 2012
    ..We have discovered that 3,3',5-triiodothyronine (T3) inhibits binding of a PIP-box sequence peptide to proliferating cell nuclear antigen (PCNA) protein by competing for the same binding site, as evidenced by the co-crystal structure of ..
  45. ncbi PCNA on the crossroad of cancer
    Ivaylo Stoimenov
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden
    Biochem Soc Trans 37:605-13. 2009
    ....
  46. pmc Interplay between mismatch repair and chromatin assembly
    Barbara Schöpf
    Institute of Molecular Cancer Research, University of Zurich, Winterthurerstasse 190, CH 8057 Zurich, Switzerland
    Proc Natl Acad Sci U S A 109:1895-900. 2012
    ..We postulated that the balance between MMR and chromatin assembly might be governed by proliferating cell nuclear antigen (PCNA), the processivity factor of replicative DNA polymerases, which is loaded at DNA termini and ..
  47. ncbi NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol η-dependent translesion DNA synthesis
    Hiromi Yanagihara
    Radiation Biology Center, Kyoto University, Kyoto 606 8501, Japan
    Mol Cell 43:788-97. 2011
    ..Thus, in addition to chromosomal break repair, NBS1 plays a key role in translesion DNA synthesis...
  48. pmc Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis
    Gargi Ghosal
    Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 287:34225-33. 2012
    DNA damage-induced proliferating cell nuclear antigen (PCNA) ubiquitination serves as the key event mediating post-replication repair...
  49. 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
    ..PAF15 associates with proliferating cell nuclear antigen (PCNA), and depletion of PAF15 decreases the number of cells in S phase, suggesting a role for it in ..
  50. ncbi Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks
    Sascha E Liberti
    Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
    DNA Repair (Amst) 10:73-86. 2011
    ..Our results reveal that protein domains in hEXO1 in conjunction with specific protein interactions control bi-directional routing of hEXO1 between on-going DNA replication and repair processes in living cells...
  51. pmc A universal protein-protein interaction motif in the eubacterial DNA replication and repair systems
    B P Dalrymple
    Commonwealth Scientific and Industrial Research Organisation Livestock Industries, 120 Meiers Road, Indooroopilly QLD 4068, Australia
    Proc Natl Acad Sci U S A 98:11627-32. 2001
    ..Comparison of the eubacterial, eukaryotic, and archaeal sliding clamp binding motifs suggests that the basic interactions have been conserved across the evolutionary landscape...
  52. pmc PCNA ubiquitination is important, but not essential for translesion DNA synthesis in mammalian cells
    Ayal Hendel
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    PLoS Genet 7:e1002262. 2011
    ..However, TLS polymerases can be recruited to damaged DNA also in the absence of PCNA-Ub, and perform TLS, albeit at a significantly lower efficiency and altered mutagenic specificity...
  53. pmc Recognition of SUMO-modified PCNA requires tandem receptor motifs in Srs2
    Anthony A Armstrong
    Structural Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
    Nature 483:59-63. 2012
    ..In yeast, the proliferating cell nuclear antigen PCNA (also known as Pol30) is modified by ubiquitin in response to DNA damage and by SUMO during S ..
  54. pmc Spatial and temporal cellular responses to single-strand breaks in human cells
    Satoshi Okano
    Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, 980 8575 Sendai, Japan
    Mol Cell Biol 23:3974-81. 2003
    ..b>Proliferating cell nuclear antigen and the p150 subunit of chromatin assembly factor 1 also accumulated at the SSB in a detergent-..
  55. pmc Elg1, an alternative subunit of the RFC clamp loader, preferentially interacts with SUMOylated PCNA
    Oren Parnas
    Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv, Israel
    EMBO J 29:2611-22. 2010
    ..Strains carrying mutations in both ELG1 and SRS2 exhibit a synthetic fitness defect that depends on PCNA modification. Our results underscore the importance of Elg1, Srs2 and SUMOylated PCNA in the maintenance of genomic stability...
  56. pmc Mrc1 and Srs2 are major actors in the regulation of spontaneous crossover
    Thomas Robert
    Commissariat a l Energie Atomique, UMR217 CNRS CEA DSV DRR SRMC LERA, Fontenay aux Roses, France
    EMBO J 25:2837-46. 2006
    ..in the absence of the Srs2 and Sgs1 helicases, DNA damage checkpoint proteins as well as in a mutant proliferating cell nuclear antigen (PCNA) and found that they all contribute to genome stability...
  57. ncbi The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA
    S Waga
    Cold Spring Harbor Laboratory, New York 11724
    Nature 369:574-8. 1994
    ..Thus, during p53-mediated suppression of cell proliferation, p21 and PCNA may be important for coordinating cell-cycle progression, DNA replication and repair of damaged DNA...
  58. pmc Human ELG1 regulates the level of ubiquitinated proliferating cell nuclear antigen (PCNA) through Its interactions with PCNA and USP1
    Kyoo Young Lee
    Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 285:10362-9. 2010
    The level of monoubiquitinated proliferating cell nuclear antigen (PCNA) is closely linked with DNA damage bypass to protect cells from a high level of mutagenesis...
  59. pmc Mechanism of CRL4(Cdt2), a PCNA-dependent E3 ubiquitin ligase
    Courtney G Havens
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 25:1568-82. 2011
    ..In this review, we discuss our current understanding of the molecular mechanism of substrate recognition by CRL4(Cdt2) and how this E3 ligase helps to maintain genome integrity...
  60. ncbi Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage
    Patricia L Kannouche
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom
    Mol Cell 14:491-500. 2004
    ..Our findings provide an attractive mechanism by which monoubiquitination of PCNA might mediate the polymerase switch...
  61. ncbi Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA
    Parker L Andersen
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5
    Cell Res 18:162-73. 2008
    ..Interestingly, in budding yeast, these two pathways are mediated by sequential modifications of the proliferating cell nuclear antigen (PCNA) by two ubiquitination complexes Rad6-Rad18 and Mms2-Ubc13-Rad5...
  62. pmc Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks
    Akira Motegi
    Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 105:12411-6. 2008
    ..In yeast, one branch of PRR involves proliferating cell nuclear antigen (PCNA) polyubiquitination mediated by the Rad5-Ubc13-Mms2 complex that allows bypass of DNA lesion ..
  63. 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
    ..Mutational analysis suggested that in addition to the PCNA binding domain, its flanking regions are also important for recognition by Cul4-DDB1(Cdt2). Our findings provide a new aspect of proteolytic control of p21 during the cell cycle...
  64. pmc The HARP-like domain-containing protein AH2/ZRANB3 binds to PCNA and participates in cellular response to replication stress
    Jingsong Yuan
    Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Mol Cell 47:410-21. 2012
    ..Thus, this study not only demonstrates the in vivo functions of AH2, but also reveals a common feature of this new subfamily of proteins with annealing activity...
  65. pmc Recognition of the ring-opened state of proliferating cell nuclear antigen by replication factor C promotes eukaryotic clamp-loading
    John A Tainer
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, MB4, La Jolla, California 92037, USA
    J Am Chem Soc 132:7372-8. 2010
    b>Proliferating cell nuclear antigen (PCNA, sliding clamp) is a toroidal-shaped protein that encircles DNA and plays a pivotal role in DNA replication, modification and repair...
  66. pmc The non-canonical protein binding site at the monomer-monomer interface of yeast proliferating cell nuclear antigen (PCNA) regulates the Rev1-PCNA interaction and Polζ/Rev1-dependent translesion DNA synthesis
    Neeru M Sharma
    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
    J Biol Chem 286:33557-66. 2011
    ..The proliferating cell nuclear antigen (PCNA), the auxiliary factor of nuclear DNA polymerases, plays an important role in regulating the ..
  67. ncbi Roles of sequential ubiquitination of PCNA in DNA-damage tolerance
    Weiwei Zhang
    College of Life Sciences, Capital Normal University, Beijing 100048, China
    FEBS Lett 585:2786-94. 2011
    ..budding yeast is achieved through sequential ubiquitination of DNA polymerase processivity factor, proliferating cell nuclear antigen (PCNA)...
  68. pmc Reversal of PCNA ubiquitylation by Ubp10 in Saccharomyces cerevisiae
    Alfonso Gallego-Sánchez
    Instituto de Biologia Molecular y Celular del Cancer, Universidad de Salamanca CSIC, Salamanca, Spain
    PLoS Genet 8:e1002826. 2012
    ..Finally, we report that Ubp10 counteracts Rad18 E3-ubiquitin ligase activity on PCNA at lysine 164 in such a manner that deregulation of Ubp10 expression causes tolerance impairment and MMS hypersensitivity...
  69. ncbi Ubiquitin-binding domains and their role in the DNA damage response
    Kay Hofmann
    Bioinformatics Group, Miltenyi Biotec GmbH, Friedrich Ebert Strasse 68, 51429 Bergisch Gladbach, Germany
    DNA Repair (Amst) 8:544-56. 2009
    ..For several repair pathways, current knowledge of the events downstream of the ubiquitin mark is sketchy. A closer look at orphan UBD proteins might lead to the identification of missing pieces in the DNA response puzzle...
  70. ncbi A ubiquitin-binding motif in the translesion DNA polymerase Rev1 mediates its essential functional interaction with ubiquitinated proliferating cell nuclear antigen in response to DNA damage
    Adam Wood
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    J Biol Chem 282:20256-63. 2007
    During normal DNA replication, the proliferating cell nuclear antigen (PCNA) enhances the processivity of DNA polymerases at the replication fork...
  71. pmc Dysregulation of DNA polymerase κ recruitment to replication forks results in genomic instability
    Mathew Jk Jones
    Department of Biochemistry, New York University School of Medicine, New York, NY, USA
    EMBO J 31:908-18. 2012
    ..Moreover, artificial tethering of Polκ to proliferating cell nuclear antigen (PCNA) circumvents the need for its ubiquitin-binding domain in the promotion of genomic instability...
  72. ncbi Y-family DNA polymerases in mammalian cells
    Caixia Guo
    Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9072, USA
    Cell Mol Life Sci 66:2363-81. 2009
    ....
  73. ncbi Regulation of translesion synthesis DNA polymerase eta by monoubiquitination
    Marzena Bienko
    Institute of Biochemistry II, Goethe University Medical School, Theodor Stern Kai 7, D 60590 Frankfurt am Main, Germany
    Mol Cell 37:396-407. 2010
    ..Our work shows how monoubiquitination can either positively or negatively regulate the assembly of a protein complex, depending on which substrates are targeted by ubiquitin...
  74. ncbi Architecture and assembly of poly-SUMO chains on PCNA in Saccharomyces cerevisiae
    Hanna Windecker
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK
    J Mol Biol 376:221-31. 2008
    Posttranslational modifications of proliferating cell nuclear antigen (PCNA), the eukaryotic processivity clamp for DNA polymerases, regulate the pathways by which replication problems are resolved...
  75. pmc Structural basis for novel interactions between human translesion synthesis polymerases and proliferating cell nuclear antigen
    Asami Hishiki
    International Graduate School of Arts and Sciences, Yokohama City University, 1 7 29 Suehiro cho, Tsurumi ku, Yokohama 230 0045, Japan
    J Biol Chem 284:10552-60. 2009
    ..These enzymes show preferential bypass for different lesions. Proliferating cell nuclear antigen (PCNA), which functions as a sliding clamp for the replicative polymerase Poldelta, also interacts ..
  76. pmc Structure of the Siz/PIAS SUMO E3 ligase Siz1 and determinants required for SUMO modification of PCNA
    Ali A Yunus
    Sloan Kettering Institute, New York, NY 10065, USA
    Mol Cell 35:669-82. 2009
    ..SUMO thioester, while the PINIT domain is essential for redirecting SUMO conjugation to the proliferating cell nuclear antigen (PCNA) at lysine 164, a nonconsensus lysine residue that is not modified by the SUMO E2 in the ..
  77. pmc Mechanistic analysis of PCNA poly-ubiquitylation by the ubiquitin protein ligases Rad18 and Rad5
    Joanne L Parker
    Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, Herts, UK
    EMBO J 28:3657-66. 2009
    ..Our results provide information about a unique conjugation mechanism that appears to be specialised for a regulatable pattern of dual modification...
  78. pmc Structure of monoubiquitinated PCNA and implications for translesion synthesis and DNA polymerase exchange
    Bret D Freudenthal
    Department of Biochemistry, University of Iowa College of Medicine, Iowa City, Iowa, USA
    Nat Struct Mol Biol 17:479-84. 2010
    ..In eukaryotes this polymerase exchange requires proliferating cell nuclear antigen (PCNA) monoubiquitination...
  79. pmc Srs2 overexpression reveals a helicase-independent role at replication forks that requires diverse cell functions
    Ana María León Ortiz
    Recombination and Genome Instability, Institut Curie Centre de Recherche, CNRS UMR, Universite Pierre et Marie Curie, Paris, France
    DNA Repair (Amst) 10:506-17. 2011
    ..This helicase-independent function is responsible for the negative interactions with DNA metabolism genes and for the toxicity of SRS2 overexpression in many of the diverse cellular pathways revealed in our screens...
  80. pmc Differential roles for DNA polymerases eta, zeta, and REV1 in lesion bypass of intrastrand versus interstrand DNA cross-links
    J Kevin Hicks
    Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109 2200, USA
    Mol Cell Biol 30:1217-30. 2010
    ....
  81. ncbi Regulating post-translational modifications of the eukaryotic replication clamp PCNA
    Helle D Ulrich
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, EN6 3LD, United Kingdom
    DNA Repair (Amst) 8:461-9. 2009
    Modifications of the eukaryotic sliding clamp, proliferating cell nuclear antigen (PCNA), by ubiquitin and the ubiquitin-related protein SUMO, are well known to influence the choice of pathways for the processing of DNA lesions during ..
  82. ncbi The post-translational modifications of proliferating cell nuclear antigen: acetylation, not phosphorylation, plays an important role in the regulation of its function
    Stanislav N Naryzhny
    Department of Research, Northeastern Ontario Regional Cancer Centre, 41 Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada
    J Biol Chem 279:20194-9. 2004
    The diverse function of proliferating cell nuclear antigen (PCNA) is thought to be due, in large part, to post-translational modifications...
  83. pmc Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis
    Hideo Nishitani
    Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Higashi ku, Fukuoka, Japan
    EMBO J 25:1126-36. 2006
    ..PCNA is essential for Cul4- but not Skp2-directed degradation during DNA replication and following ultraviolet-irradiation. Our data unravel multiple distinct pathways regulating Cdt1 to block re-replication...
  84. pmc Controlling the subcellular localization of DNA polymerases iota and eta via interactions with ubiquitin
    Brian S Plosky
    Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2725, USA
    EMBO J 25:2847-55. 2006
    ..that both polymerases interact noncovalently with free polyUb chains, as well as mono-ubiquitinated proliferating cell nuclear antigen (Ub-PCNA)...
  85. ncbi Expression of proliferating cell nuclear antigen in ameloblastomas and odontogenic cysts
    A Piattelli
    Dental School, University of Chieti, Italy
    Oral Oncol 34:408-12. 1998
    ..b>Proliferating cell nuclear antigen (PCNA) has been used for the evaluation of the proliferative ability of many lesions...
  86. pmc Ubiquitinated proliferating cell nuclear antigen activates translesion DNA polymerases eta and REV1
    Parie Garg
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 102:18361-6. 2005
    ..to DNA damage, the Rad6/Rad18 ubiquitin-conjugating complex monoubiquitinates the replication clamp proliferating cell nuclear antigen (PCNA) at Lys-164...
  87. ncbi Tyrosine phosphorylation controls PCNA function through protein stability
    Shao Chun Wang
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Nat Cell Biol 8:1359-68. 2006
    The proliferating cell nuclear antigen (PCNA) is an essential protein for DNA replication and damage repair. How its function is controlled remains an important question...
  88. pmc RAD18-mediated ubiquitination of PCNA activates the Fanconi anemia DNA repair network
    Liyi Geng
    Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    J Cell Biol 191:249-57. 2010
    ..damage-activated E3 ubiquitin ligase, also participates in ID complex activation by ubiquitylating proliferating cell nuclear antigen (PCNA) on Lys164, an event required for the recruitment of FANCL to chromatin...
  89. pmc XRCC1 and PCNA are loading platforms with distinct kinetic properties and different capacities to respond to multiple DNA lesions
    Oliver Mortusewicz
    Ludwig Maximilians University Munich, Department of Biology II, 82152 Planegg Martinsried, Germany
    BMC Mol Biol 8:81. 2007
    ..We investigated the dynamics of XRCC1 and PCNA that act as molecular loading platforms and play a central role in this coordination...
  90. pmc Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination
    Ildiko Unk
    Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvari korut 62, H 6726, Szeged, Hungary
    Proc Natl Acad Sci U S A 105:3768-73. 2008
    ..ubiquitin-conjugating enzyme complexes and promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen at its Lys-164 residue...
  91. pmc DNA damage-induced ubiquitylation of RFC2 subunit of replication factor C complex
    Junya Tomida
    Radiation Biology Center, and Institute for Virus Research, Kyoto University, Kyoto 606 8501, Japan
    J Biol Chem 283:9071-9. 2008
    ..b>Proliferating cell nuclear antigen (PCNA; a homotrimeric protein that encircles double-stranded DNA to function as a sliding clamp for ..
  92. pmc Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival
    Véronique Witko-Sarsat
    Institut National de la Santé et de la Recherche Médicale Unité 1016, 75014 Paris, France
    J Exp Med 207:2631-45. 2010
    ..In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells...
  93. pmc Phosphorylated Rad18 directs DNA polymerase η to sites of stalled replication
    Tovah A Day
    Department of Genetics and Genomics and 2 Center for Human Genetics, Boston University School of Medicine, Boston, MA 02118, USA
    J Cell Biol 191:953-66. 2010
    ..Rad18 guides DNA Polymerase eta (Polη) to sites of replication fork stalling and mono-ubiquitinates proliferating cell nuclear antigen (PCNA) to facilitate binding of Y family trans-lesion synthesis (TLS) DNA polymerases during TLS...
  94. pmc Replication protein A-directed unloading of PCNA by the Ctf18 cohesion establishment complex
    Göran O Bylund
    Department of Biochemistry, Washington University School of Medicine, 660 S Euclid, St Louis, Missouri 63110, USA
    Mol Cell Biol 25:5445-55. 2005
    ....
  95. ncbi SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase
    Boris Pfander
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Nature 436:428-33. 2005
    ..Two main bypasses are controlled by ubiquitin modification of proliferating cell nuclear antigen (PCNA), a homotrimeric DNA-encircling protein that functions as a polymerase processivity factor and ..
  96. ncbi Characterization of the two small subunits of Saccharomyces cerevisiae DNA polymerase delta
    K J Gerik
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 273:19747-55. 1998
    ..The POL32 gene product binds proliferating cell nuclear antigen. A gel filtration analysis showed that Pol32p is a dimer in solution...
  97. ncbi Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function
    Satya Prakash
    Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555 1061, USA
    Annu Rev Biochem 74:317-53. 2005
    ..b>Proliferating cell nuclear antigen (PCNA) provides the central scaffold to which TLS polymerases bind for access to the replication ..
  98. pmc Structural determinant for switching between the polymerase and exonuclease modes in the PCNA-replicative DNA polymerase complex
    Hirokazu Nishida
    Central Research Laboratory, Hitachi Ltd, 1 280 Higashi Koigakubo, Kokubunji, Tokyo 185 8601, Japan
    Proc Natl Acad Sci U S A 106:20693-8. 2009
    b>Proliferating cell nuclear antigen (PCNA) is responsible for the processivity of DNA polymerase...
  99. pmc The crystal structure of Haloferax volcanii proliferating cell nuclear antigen reveals unique surface charge characteristics due to halophilic adaptation
    Jody A Winter
    Institute of Genetics, University of Nottingham, Queen s Medical Centre, Nottingham, NG7 2UH, UK
    BMC Struct Biol 9:55. 2009
    ..b>Proliferating cell nuclear antigen (PCNA) is a fundamental protein involved in maintaining genome integrity, with roles in both DNA ..
  100. pmc Dual roles of the SUMO-interacting motif in the regulation of Srs2 sumoylation
    Peter Kolesar
    Department of Biology, National Centre for Biomolecular Research, Masaryk University, 62500 Brno, Czech Republic
    Nucleic Acids Res 40:7831-43. 2012
    ..Our findings suggest a potential mechanism for the equilibrium of sumoylated and PCNA-bound pools of Srs2 in cells...
  101. ncbi The flavonoid component isorhamnetin in vitro inhibits proliferation and induces apoptosis in Eca-109 cells
    Gang Ma
    The Medicine Biology Laboratory of Life Science, College of Sichuan University, Chengdu, Sichuan Province 610041, People s Republic of China
    Chem Biol Interact 167:153-60. 2007
    ..In conclusion, isorhamnetin appears to be a potent drug against esophageal cancer due to its in vitro potential to not only inhibit proliferation but also induce apoptosis of Eca-109 cells...

Research Grants63

  1. The Molecular Mechanisms by which the Paf Oncogene Mediates Hematopoiesis
    Lisa K Denzin; Fiscal Year: 2013
    ..We recently showed that the highly conserved 15 kDa Proliferating Cell Nuclear Antigen (PCNA) associated factor (Paf) is a novel and essential HSC cell cycle regulator...
  2. Understanding the role of PCNA in DNA mismatch repair subpathways
    EVA MARIE GOELLNER; Fiscal Year: 2013
    ..PCNA (Proliferating Cell Nuclear Antigen) is an integral part of the MMR pathway, although its mechanistic roles are not completely ..
  3. The dynamics of DNA methylation in normal and cancer cells
    GREGORY ADAM HORWITZ; Fiscal Year: 2011
    ..DNMT1 is recruited to replication foci in part through its interaction with proliferating cell nuclear antigen (PCNA), and in part by directly interacting with UHRF1...
  4. Targeting of AID Mutagenic Activity
    David Kazadi; Fiscal Year: 2013
    ..In this respect, we propose in our first aim that proliferating cell nuclear antigen (PCNA), a DNA clamp also usually found in the context of replication, helps AID recruit these other ..
  5. Understanding the Biological Function of MCM 10
    Anja Katrin Bielinsky; Fiscal Year: 2013
    ..the replicative helicase, DNA polymerase (pol)- 1/primase and the homo-trimeric replication clamp, proliferating cell nuclear antigen (PCNA)...
  6. Increased Plasma Nitrite, Tissue Oxygenation and Functional Changes in PAD
    Jason David Allen; Fiscal Year: 2013
    ..via biopsy) (a) angiogenesis and arteriogenesis (capillary density with surrounding pericytes, proliferating cell nuclear antigen, and apoptosis) and oxidative capacity (fiber type composition, citrate synthase activity), and (b) ..
  7. FEN-1 and PCNA Complexes and Human Genome Stability
    John A Tainer; Fiscal Year: 2013
    ..are furthermore aided by their partner protein, the processivity factor for DNA polymerase, termed proliferating cell nuclear antigen (PCNA)...
  8. Curcumin chemoprevention in familial adenomatous polyposis
    Francis M Giardiello; Fiscal Year: 2013
    ..of epithelial proliferation (ornithine decarboxylase, polyamines and immunohistochemistry for proliferating cell nuclear antigen), apoptosis (apoptotic index by morphologic measurement and TUNEL assay), and cyclooxygenase- 2 ..
  9. Mechanism of PCNA Polyubiquitination
    CHRISTOPHER EDWARD BERNDSEN; Fiscal Year: 2010
    ..Commitment to error-free damage tolerance hinges on polyubiquitin modification of the proliferating cell nuclear antigen (PCNA)...
  10. A MULTIDISCIPLINARY APPROACH TO PEPTIDE-BASED ANTAGONISTS OF PCNA
    Zhihao Zhuang; Fiscal Year: 2011
    ..we describe a multidisciplinary approach to develop novel peptide-based antagonists of the proliferating cell nuclear antigen (PCNA)...
  11. SUMOylation and ubiquitylation of PCNA in recombination and translesion synthesis
    M Todd Washington; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Post-translational modifications of proliferating cell nuclear antigen (PCNA) are essential for maintaining genome stability...
  12. Association between the Y chromosome and androgens
    Kathryn Sandberg; Fiscal Year: 2007
    ..Cell proliferation and death will be determined by proliferating cell nuclear antigen and Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End labeling (TUNEL), respectively...
  13. Hormonal Regulation of the Cervix During Pregnancy
    ORRIN SHERWOOD; Fiscal Year: 2006
    ..of 5-bromo-2-deoxyuridine (BrdU) into proliferating cells and also by measuring the expression of proliferating cell nuclear antigen (PCNA). RU 486 induces delivery and promotes cervical softening at term in women and other species...
  14. TESTOSTERONE REPLACEMENT & PHYSICAL FUNCTION IN HIV+MEN
    Shalender Bhasin; Fiscal Year: 2005
    ..Phosphorylated retinoblastoma protein and proliferating cell nuclear antigen (PCNA) will be used as markers of satellite cell cycle events...
  15. RECTAL MUCOSAL PROLIFERATION INDICES--EFFECTS OF CALCIUM
    John Baron; Fiscal Year: 1992
    ..subsequent assessment of labelling indices (and related measures) based on bromodeoxyuridine and proliferating cell nuclear antigen. The primary analysis will focus on (1) the difference in labelling indices at year 1 between ..
  16. GENISTEIN IN INVESTIGATIVE AND CLINICAL DERMATOLOGY
    Huachen Wei; Fiscal Year: 2005
    ..In addition, certain molecular endpoints such as 8-OHdG, pyrimidine dimers, p53 and proliferating cell nuclear antigen (PCNA) expression will be detected in human skin biopsies and the reconstituted 3-dimensional human ..
  17. FUNCTION OF PCNA IN CELLULAR DNA REPAIR
    Yoshihiro Matsumoto; Fiscal Year: 2001
    ..My laboratory, was first to identify an alternative pathway which requires proliferating cell nuclear antigen (PCNA) as an essential factor...
  18. FUNCTION OF QUIESCENT CELLS IN PEDIATRIC LEUKEMIA
    Michael Andreeff; Fiscal Year: 1992
    ..If successful, these studies will introduce cytokines into chemotherapeutic regimen for the treatment of pediatric All and will hopefully improve the remission duration for children with poor risk and relapsed ALL...
  19. TUMOR HOST RELATIONSHIPS IN HUMAN LYMPHOMAS IN VIVO
    Roger Warnke; Fiscal Year: 1993
    ..Long-term goals are to devise a more reproducible, clinically predictive classification of lymphomas. Such an in vivo evaluation of tumor host relationships should provide valuable insights in lymphoma immunobiology...
  20. STRUCTURE/FUNCTION OF A DNA REPAIR ENDONUCLEASE
    Binghui Shen; Fiscal Year: 2001
    ..and cleavage; to analyze the structural elements responsible for protein-protein interaction with proliferating cell nuclear antigen; and to map the nuclear localization signal in FEN-1...
  21. MOLECULAR CHARACTERIZATION OF MCLI PCNA INTERACTION
    Kenichi Fujise; Fiscal Year: 2003
    ..Fujise discovered a novel interaction between MCL1 and PCNA (Proliferating cell nuclear antigen)...
  22. P53 IN ASBESTOS INDUCED LUNG DISEASE
    Gilbert Morris; Fiscal Year: 2000
    ..Our observations of lung repair will be correlated with expression of the proliferating cell nuclear antigen, PCNA, an essential DNA replication and repair protein that is also expressed at the sites of fiber ..
  23. SOY ISOFLAVONES AND CELL PROLIFERATION
    Roberd Bostick; Fiscal Year: 2000
    ..Cell proliferation will be assessed by immunostaining for proliferating cell nuclear antigen, and proliferating cells will be quantified by detailed histomorphometric analysis...
  24. MATERNAL MRNA LOCALIZATIONS IN A DETERMINATE EGG
    WILLIAM JEFFERY; Fiscal Year: 2002
    ..crescent (YC) and Uro-1 RNAs, which are localized in the myoplsam (muscle-forming region), and proliferating cell nuclear antigen (PCNA) mRNA, which is localized in the ectoplasm (epidermal and neural-forming region) of ascidian ..
  25. Involvement of APC in DNA Repair
    Satya Narayan; Fiscal Year: 2006
    ..data indicate that the APC protein interacts with the DNA base excision repair (BER) proteins, proliferating cell nuclear antigen (PCNA) and apurinic/apyrimidinic endonuclease (APE), and the cell cycle kinase inhibitor protein, ..
  26. Tumor suppressor adenomatous polyposis coli and breast carcinogenesis
    Satya Narayan; Fiscal Year: 2007
    ..preliminary data indicate that APC protein interacts with base excision repair proteins, including proliferating cell nuclear antigen (PCNA) and apurinic/apydmidinic endonudease (APE)...
  27. MARKERS OF FUTURE BREAST CANCER RISK IN BIOPSIED WOMEN
    William Barlow; Fiscal Year: 1993
    ..characteristics (histologic type, S-phase fraction, and ploidy) and control mechanisms (receptors, proliferating cell nuclear antigen (PCNA), oncogene expression, and cathepsin-D)...
  28. OLIGODENDROGLIAL REPOPULATION OF DEMYELINATED LESIONS
    REGINA ARMSTRONG; Fiscal Year: 1999
    ..In addition, immunohistochemical detection of proliferating cell nuclear antigen will assess the proliferative response to demyelination...
  29. Application of TiO2-DNA nanocomposites to Cancer Cells
    Gayle Woloschak; Fiscal Year: 2006
    ..As a model gene target for nanocomposite cleavage we will use Proliferating Cell Nuclear Antigen (PCNA), a housekeeping gene that is necessary for cell survival and that is overexpressed in a large ..
  30. INTERFERON-INDUCED ALTERATIONS IN CELLS
    IGOR TAMM; Fiscal Year: 1990
    ..For these studies we will use mouse BALB/c 3T3 (clone A31) cells and purified mouse Alpha/Beta or Beta IFNs, and human diploid skin fibroblasts (0038A cells) and human Beta IFN...
  31. Androgenic Inactivation of FKHR in Prostate Cancer
    Donald Tindall; Fiscal Year: 2006
    ..are mediated in part by androgen-induced increases in proliferation-promoting proteins, such as proliferating cell nuclear antigen (PCNA), cyclin-dependent kinases 2 and 4, as well as decreases in cell cycle inhibitors, such as ..
  32. Neural Stem Cell Survival and Function in Aging Mice an*
    STEVEN PRUITT; Fiscal Year: 2004
    ..Additionally, we will test the utility of expression of the DNA polymerase subunit proliferating cell nuclear antigen (PCNA) as a surrogate for nucleotide analog incorporation in defining the proliferative progenitor ..
  33. Replication Through CAG Trinucleotide Repeat Tracts
    DENNIS LIVINGSTON; Fiscal Year: 2004
    ..detailed studies on mutations of the DNA helicase, DNA polymerase, DNA ligase, flap endonuclease and proliferating cell nuclear antigen (PCNA) we will define the mechanism by which flaps of DNA give rise to tract expansions...
  34. Role of p21 in antidepressant-induced neurogenesis
    Vera Chesnokova; Fiscal Year: 2009
    ..of cells expressing nuclear protein antigen NeuN, a marker for neurons, and with the induction of proliferating cell nuclear antigen PCNA, a marker of cellular proliferation...
  35. HYPOXIA AND GENE EXPRESSION IN HUMAN TUMORS
    James Raleigh; Fiscal Year: 2003
    ..Pimonidazole binding will be used to identify regions of hypoxia; proliferating cell nuclear antigen (PCNA) will be used to locate regions of proliferation; and, involucrin will be used to identify ..
  36. Development of a Cancer Specific PCNA Tumor Marker Immu*
    Cha Mei Tang; Fiscal Year: 2004
    ..innovative cancer screening and diagnostic test based on the molecular tumor marker cancer specific proliferating cell nuclear antigen (csPCNA)...
  37. Pharmacologically Enhanced Fracture Repair by Statins
    Gloria Gutierrez; Fiscal Year: 2004
    ..of proliferating cell organization in the developing callus utilizing monoclonal antibodies against proliferating cell nuclear antigen. Aim 2" Evaluate the effect of Iovastatin on callus formation, maturation, and fracture healing ..
  38. EGCG intervention in a Sjogren?s Syndrome model prior to disease onset
    Stephen Hsu; Fiscal Year: 2009
    ..Our results from a pilot study indicate that EGCG suppresses the expression of ductal epithelial proliferating cell nuclear antigen (PCNA) and Ki- 67, markers for cell proliferation, starting at early age prior to disease onset...
  39. BREAST CANCER ETIOLOGY--P53 GAIN OF FUNCTION MUTATIONS
    Sumitra Deb; Fiscal Year: 2000
    ..The presence of p53 mutations and overexpression of the epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) indicate poor prognosis in breast cancer...
  40. Links between Mismatch Repair and Replication
    Hernan Flores Rozas; Fiscal Year: 2005
    ..demonstrated that the mismatch recognition complexes MSH2p-MSH6p and MSH2p-MSH3p associate with the proliferating cell nuclear antigen (PCNA), a protein that plays a central role on DNA replication as a sliding clamp that enhances the ..
  41. The Multiple Partners of Mismatch Repair MutL Homologs
    Shannon Holmes; Fiscal Year: 2005
    The objectives of this research are to discover the proliferating cell nuclear antigen (PCNA) binding site on yeast MutLalpha, a component of the mismatch repair machinery, and to discover if MutLalpha can interact with the 9-1-1 complex, ..
  42. RIBOZYMES FOR THE PREVENTION OF RESTENOSIS AFTER PTCA
    Jack Barber; Fiscal Year: 2000
    Chimeric ribozyme-based therapeutics targeting Proliferating Cell Nuclear Antigen (PCNA) have been identified and shown to prevent vascular smooth muscle cell proliferation that is a major contributing factor in restenosis...
  43. EXPANSION OF PANCREATIC ISLETS USING A NOVEL BIOMATERIAL
    ERIK WOODS; Fiscal Year: 2002
    ..who will serve as their Phase III partner for both of these products. These products will have importance in enhancing islet transplantation as a treatment and/or cure for type I diabetes. PROPOSED COMMERCIAL APPLICATION: Not available ..
  44. DEVELOPMENT AND EVALUATION OF A NOVEL CANCER BIOMARKER
    Linda Malkas; Fiscal Year: 2003
    ..accompanied by a significant alteration of a specific protein component of the synthesome, namely, proliferating cell nuclear antigen (PCNA)...
  45. EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS IN ANIMAL MOD
    Clinton Grubbs; Fiscal Year: 2000
    ..g. cell cycle proteins (e.g. PCNA),cyclin levels and telomerase activity). ..
  46. FIDELITY OF DNA SYNTHESIS IN HEMATOPOEITIC TISSUES
    ANTERO SO; Fiscal Year: 2001
    ..that the small subunit is essential for functional interaction of DNA polymerase d with the proliferating cell nuclear antigen (PCNA) and thus for highly processive DNA synthesis...
  47. EXPANSION OF PANCREATIC ISLETS USING NOVEL BIOMATERIAL
    John Critser; Fiscal Year: 1999
    ..Development of a product that will promote the proliferation of pancreatic islets in vitro would enhance the use of islet transplantation as a cure for the disease. ..
  48. EFFICACY OF CHEMOPREVENTIVE AGENTS IN ANIMAL MODELS
    Clinton Grubbs; Fiscal Year: 1999
    ..g. cell cycle proteins (e.g. PCNA),cyclin levels and telomerase activity). ..
  49. Structure Determination of the Polymerase alpha-primase
    DEWIGHT WILLIAMS; Fiscal Year: 2006
    ..which is performed by the polymerase delta in conjunction with the processivity factor PCNA (Proliferating Cell Nuclear Antigen)...
  50. MECHANISMS FOR CHEMOPREVENTION OF COLON CANCER
    CHINTHALAPALLY RAO; Fiscal Year: 2004
    ..Tissue distribution and comparative metabolism studies of curcumin and PEMC will be studied with synthetic [3H] curcumin and [3H]-PEMC in vivo in male F-344 rats. ..
  51. PREVENTION OF COLORECTAL CANCER BY iNOS AND COX-2 SELECTIVE INHIBITORS
    CHINTHALAPALLY RAO; Fiscal Year: 2008
    ..abstract_text> ..
  52. In Vitro Cancer Prevention Biomarker Development
    Eugene Elmore; Fiscal Year: 2004
    ..Using cluster analysis, we will determine the global gene expression changes induced by each agent. The strength of the proposed approach lies in the high quality data that has already determined from the HEC Assay. ..
  53. NOVEL THERAPIES FOR ACETAMINOPHEN TOXICITY
    Laura James; Fiscal Year: 2004
    ..abstract_text> ..
  54. ALVEOLAR TYPE II CELL GROWTH IN INJURY
    RANDOLPH HASTINGS; Fiscal Year: 2003
    ..The project will evaluate the potential use of PTHrP-related therapeutic interventions that might speed or improve recovery following silica-induced lung injury. ..
  55. Identification of Green Tea Polyphenol-Targeted Genes
    Stephen Hsu; Fiscal Year: 2004
    ..Data generated from this proposal may reveal novel drug targets for treatment of head and neck cancer. ..
  56. TRANSFORMING GROWTH FACTOR BETA IN OXIDANT LUNG INJURY
    MICHAEL O REILLY; Fiscal Year: 2002
    ..These studies are significant because understanding how ROS injure and kill pulmonary epithelial cells is critically important for improving clinical therapies that rely on supplemental oxygen. ..
  57. Estradiol Metabolites for Treatment of Pulmonary Hypertension
    Stevan Tofovic; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  58. Biology of the Primate Ovarian Surface Epithelium
    Jay W Wright; Fiscal Year: 2011
    ..g. infertility) and pathology (e.g. tumorigenesis). The result of this project will generate a comprehensive tissue archive to be used in future studies and collaborations with other investigators. ..
  59. C/EBP alpha in Aging Liver
    Nikolai Timchenko; Fiscal Year: 2009
    ..Based on data obtained in this project, we are planning to start developing a strategy to correct liver proliferation in elderly. ..
  60. Colon and liver anticarcinogenicity by acetaminophen
    Gary Williams; Fiscal Year: 2004
    ..In addition, these experiments will provide support for the epidemiological observations of reduced cancer risk associated with the use of APAP. ..
  61. MICROARRAY ANALYSIS OF RETINAL DEGENERATION IN MICE
    Caroline Zeiss; Fiscal Year: 2007
    ..Colin Barnstable, Professor of Neurobiology and Ophthalmology, who is an internationally recognized molecular biologist using mouse models of retinal development and degeneration. ..
  62. Stretch and Vitamin A Effects on Alveolar Formation
    KURT ALBERTINE; Fiscal Year: 2009
    ..We will test the hypothesis that the promoter regions of our 3 target genes are retinoid responsive. Thus, this project will provide novel mechanistic insights about alveolar formation and its dysregulation in CLD. ..