dna helicases

Summary

Summary: Proteins that promote unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. EC 5.99.-.

Top Publications

  1. ncbi The Bloom's syndrome helicase suppresses crossing over during homologous recombination
    Leonard Wu
    Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK
    Nature 426:870-4. 2003
  2. pmc Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres
    Peter W Lewis
    Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, 1230 York Ave, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:14075-80. 2010
  3. pmc DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors
    Yuchen Jiao
    Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 331:1199-203. 2011
  4. pmc DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase
    Katrin Paeschke
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Cell 145:678-91. 2011
  5. ncbi Pathways of mammalian replication fork restart
    Eva Petermann
    University of Birmingham, UK
    Nat Rev Mol Cell Biol 11:683-7. 2010
  6. ncbi Systematic genetic analysis with ordered arrays of yeast deletion mutants
    A H Tong
    Banting and Best Department of Medical Research, University of Toronto, Toronto ON, Canada M5G 1L6
    Science 294:2364-8. 2001
  7. ncbi Structure and mechanism of helicases and nucleic acid translocases
    Martin R Singleton
    Macromolecular Structure and Function Laboratory, The London Research Institute, London WC2A 3PX, United Kingdom
    Annu Rev Biochem 76:23-50. 2007
  8. pmc BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures
    Y Wang
    Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:927-39. 2000
  9. pmc The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3
    Pascal Drané
    IGMBC Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch F 67400, France
    Genes Dev 24:1253-65. 2010
  10. pmc SF1 and SF2 helicases: family matters
    Margaret E Fairman-Williams
    Center for RNA Molecular Biology and Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    Curr Opin Struct Biol 20:313-24. 2010

Detail Information

Publications329 found, 100 shown here

  1. ncbi The Bloom's syndrome helicase suppresses crossing over during homologous recombination
    Leonard Wu
    Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK
    Nature 426:870-4. 2003
    ..These results have wider implications for our understanding of the process of homologous recombination and the mechanisms that exist to prevent tumorigenesis...
  2. pmc Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres
    Peter W Lewis
    Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, 1230 York Ave, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:14075-80. 2010
    ..These data demonstrate that Daxx functions as an H3.3-specific chaperone and facilitates the deposition of H3.3 at heterochromatin loci in the context of the ATRX-Daxx complex...
  3. pmc DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors
    Yuchen Jiao
    Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 331:1199-203. 2011
    ..We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors...
  4. pmc DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase
    Katrin Paeschke
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Cell 145:678-91. 2011
    ..These data suggest that G4 structures form in vivo and that they are resolved by Pif1 to prevent replication fork stalling and DNA breakage...
  5. ncbi Pathways of mammalian replication fork restart
    Eva Petermann
    University of Birmingham, UK
    Nat Rev Mol Cell Biol 11:683-7. 2010
    ..Different models of replication fork restart can be envisaged, based on the involvement of DNA helicases, nucleases, homologous recombination factors and the importance of DNA double-strand break formation.
  6. ncbi Systematic genetic analysis with ordered arrays of yeast deletion mutants
    A H Tong
    Banting and Best Department of Medical Research, University of Toronto, Toronto ON, Canada M5G 1L6
    Science 294:2364-8. 2001
    ..Systematic application of this approach should produce a global map of gene function...
  7. ncbi Structure and mechanism of helicases and nucleic acid translocases
    Martin R Singleton
    Macromolecular Structure and Function Laboratory, The London Research Institute, London WC2A 3PX, United Kingdom
    Annu Rev Biochem 76:23-50. 2007
    ..As a result, each superfamily is subdivided, where appropriate, on the basis of mechanistic understanding, which we hope will provide a framework for classification of new superfamily members as they are discovered and characterized...
  8. pmc BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures
    Y Wang
    Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:927-39. 2000
    ..Collectively, these results suggest that BRCA1 may function as a coordinator of multiple activities required for maintenance of genomic integrity during the process of DNA replication and point to a central role for BRCA1 in DNA repair...
  9. pmc The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3
    Pascal Drané
    IGMBC Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch F 67400, France
    Genes Dev 24:1253-65. 2010
    ..Taken together, our data demonstrate that DAXX functions as a bona fide histone chaperone involved in the replication-independent deposition of H3.3...
  10. pmc SF1 and SF2 helicases: family matters
    Margaret E Fairman-Williams
    Center for RNA Molecular Biology and Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    Curr Opin Struct Biol 20:313-24. 2010
    ..We discuss recent data in the context of this unifying view of SF1 and SF2 helicases...
  11. ncbi The SWI/SNF complex and cancer
    D Reisman
    Department of Internal Medicine, University of Michigan College of Medicine, Ann Arbor, MI 48109 0686, USA
    Oncogene 28:1653-68. 2009
    ....
  12. pmc Altered telomeres in tumors with ATRX and DAXX mutations
    Christopher M Heaphy
    Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
    Science 333:425. 2011
    ..ATRX mutations also correlate with abnormal telomeres in tumors of the central nervous system. These data suggest that an alternative telomere maintenance function may operate in human tumors with alterations in the ATRX or DAXX genes...
  13. pmc Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint
    Tony S Byun
    Department of Molecular Pharmacology, Stanford University, Stanford, CA 94305, USA
    Genes Dev 19:1040-52. 2005
    ....
  14. pmc Yeast Sen1 helicase protects the genome from transcription-associated instability
    Hannah E Mischo
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
    Mol Cell 41:21-32. 2011
    ..Based on these findings, we propose that R loop formation is a frequent event during transcription and a key function of Sen1 is to prevent their accumulation and associated genome instability...
  15. pmc Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing
    Dirk Remus
    Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms EN6 3LD, UK
    Cell 139:719-30. 2009
    ..Our work has significant implications for understanding how eukaryotic DNA replication origins are chosen and licensed, how replisomes assemble during initiation, and how unwinding occurs during DNA replication...
  16. pmc Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway
    Courtney A Lovejoy
    Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York, United States of America
    PLoS Genet 8:e1002772. 2012
    ..These attributes will facilitate the diagnosis and treatment of ALT positive human cancers...
  17. ncbi ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner
    Martin J Law
    Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
    Cell 143:367-78. 2010
    ..We show that ATRX binds G-quadruplex structures in vitro, suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated...
  18. pmc MHF1-MHF2, a histone-fold-containing protein complex, participates in the Fanconi anemia pathway via FANCM
    Thiyam Ramsing Singh
    Division of Experimental Hematology and Cancer Biology, Cincinnati Children s Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Mol Cell 37:879-86. 2010
    ..These findings reveal critical roles of the MHF1-MHF2 dimer in DNA damage repair and genome maintenance through FANCM...
  19. pmc BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair
    Amitabh V Nimonkar
    Department of Microbiology, University of California at Davis, Davis, California 95616, USA
    Genes Dev 25:350-62. 2011
    ..BLM increases the affinity of EXO1 for ends, and MRN recruits and enhances the processivity of EXO1. Our results establish two of the core machineries that initiate recombinational DNA repair in human cells...
  20. ncbi Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks
    Dana Branzei
    FIRC Institute of Molecular Oncology Foundation and Department of Biomedical Sciences and Biotechnology, Universita degli Studi di Milano, Via Adamello 16, 20139 Milan, Italy
    Cell 127:509-22. 2006
    ..Our results indicate that Ubc9- and Mms21-mediated sumoylation functions as a regulatory mechanism, different from that of replication checkpoints, to prevent pathological accumulation of cruciform structures at damaged forks...
  21. ncbi DNA replication and transcription in mammalian mitochondria
    Maria Falkenberg
    Division of Metabolic Diseases, Karolinska Institutet, Novum, SE 141 86 Stockholm
    Annu Rev Biochem 76:679-99. 2007
    ..Recent years have seen a rapid development in our molecular understanding of these machineries, but many aspects still remain unknown...
  22. pmc Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1
    Dragana Ahel
    DNA Damage Response Laboratory, Clare Hall, London Research Institute, South Mimms EN6 3LD, UK
    Science 325:1240-3. 2009
    ..Furthermore, we show that depletion or overexpression of ALC1 results in sensitivity to DNA-damaging agents. Collectively, these results provide new insights into the mechanisms by which poly(ADP-ribose) regulates DNA repair...
  23. pmc A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability
    Zhijiang Yan
    Laboratory of Genetics, National Institute of Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Mol Cell 37:865-78. 2010
    ..Thus, FANCM-MHF is an essential DNA-remodeling complex that protects replication forks from yeast to human...
  24. pmc ATRX interacts with H3.3 in maintaining telomere structural integrity in pluripotent embryonic stem cells
    Lee H Wong
    Chromosome and Chromatin Research, Murdoch Childrens Research Institute, Department of Paediatrics, University of Melbourne, Royal Children s Hospital, Parkville, Victoria 3052, Australia
    Genome Res 20:351-60. 2010
    ..These findings suggest a novel function of ATRX, working in conjunction with H3.3 and CBX5, as a key regulator of ES-cell telomere chromatin...
  25. ncbi Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone
    Rongmin Zhao
    Department of Biochemistry, Medical Sciences Building, 1 King s College Circle, University of Toronto, Toronto, ON, M5S 1A8, Canada
    Cell 120:715-27. 2005
    ..These cofactors interact physically and functionally with the conserved AAA(+)-type DNA helicases Rvb1/Rvb2, which are key components of several chromatin remodeling factors, thereby linking Hsp90 to ..
  26. ncbi The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen
    T M Gottlieb
    Wellcome CRC Institute, Cambridge, England
    Cell 72:131-42. 1993
    ..The implications of the unusual DNA binding mode and multicomponent nature of the DNA-PK are discussed...
  27. ncbi Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria
    J N Spelbrink
    Institute of Medical Technology and Tampere University Hospital, Tampere, Finland
    Nat Genet 28:223-31. 2001
    ..The mutations cluster in a region of the protein proposed to be involved in subunit interactions. The function of Twinkle is inferred to be critical for lifetime maintenance of human mtDNA integrity...
  28. pmc Polymerase dynamics at the eukaryotic DNA replication fork
    Peter M J Burgers
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 284:4041-5. 2009
    ..In the more common short flap pathway, Pol delta coordinates with the flap endonuclease FEN1 to degrade initiator RNA, whereas in the long flap pathway, RNA removal is initiated by the Dna2 nuclease/helicase...
  29. ncbi Translocation and unwinding mechanisms of RNA and DNA helicases
    Anna Marie Pyle
    Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute and Yale University, New Haven, Connecticut 06520, USA
    Annu Rev Biophys 37:317-36. 2008
    ..Through structural and single-molecule investigations, researchers are developing coherent models to explain the functions and dynamic motions of helicase enzymes...
  30. pmc Caenorhabditis elegans HIM-18/SLX-4 interacts with SLX-1 and XPF-1 and maintains genomic integrity in the germline by processing recombination intermediates
    Takamune T Saito
    Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Genet 5:e1000735. 2009
    ..elegans BLM homolog. We propose that HIM-18 facilitates processing of HR intermediates resulting from replication fork collapse and programmed meiotic DSBs in the C. elegans germline...
  31. pmc The Mcm complex: unwinding the mechanism of a replicative helicase
    Matthew L Bochman
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    Microbiol Mol Biol Rev 73:652-83. 2009
    ....
  32. pmc Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication
    Francis Fabre
    Unité mixte de recherche 217, Centre National de la Recherche Scientifique Commissariat à l Energie Atomique Département de Radiobiologie et Radiopathologie BP6, 92265 Fontenay aux Roses, France
    Proc Natl Acad Sci U S A 99:16887-92. 2002
    ..Our results suggest that Srs2 channels recombination intermediates back into the gap-filling route, whereas Sgs1Top3 and Mus81Mms4 are involved in recombination andor in replication to allow replication restart...
  33. pmc Meiotic chromosome synapsis-promoting proteins antagonize the anti-crossover activity of sgs1
    Lea Jessop
    Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
    PLoS Genet 2:e155. 2006
    ..These findings show that Sgs1 has potent meiotic anti-CO activity, which is normally antagonized by SIC/ZMM proteins. Our data reinforce previous proposals for an early separation of meiotic processes that form CO and NCO recombinants...
  34. pmc Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells
    A J Pierce
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, and Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA
    Genes Dev 15:3237-42. 2001
    ..Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results...
  35. pmc ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor
    E Citterio
    Medical Genetic Center, Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands
    Mol Cell Biol 20:7643-53. 2000
    ..CSB is the first repair protein found to play a direct role in modulating nucleosome structure. The relevance of this finding to the interplay between transcription and repair is discussed...
  36. pmc RTEL1 maintains genomic stability by suppressing homologous recombination
    Louise J Barber
    DNA Damage Response Laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms EN6 3LD, UK
    Cell 135:261-71. 2008
    ..We propose that loss of HR control after deregulation of RTEL1 may be a critical event that drives genome instability and cancer...
  37. pmc Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase
    Giordano Liberi
    F I R C Institute of Molecular Oncology Foundation, 20141, Milan, Italy
    Genes Dev 19:339-50. 2005
    ..Our findings might contribute to explaining some of the recombination defects of BLM cells...
  38. pmc The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks
    Katsuhiro Hanada
    Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands
    EMBO J 25:4921-32. 2006
    ..We propose that Mus81-Eme1- and Rad54-mediated homologous recombination are involved in the same DNA replication-dependent ICL repair pathway...
  39. pmc A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication
    Cecile Evrin
    DNA replication Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom
    Proc Natl Acad Sci U S A 106:20240-5. 2009
    ..The organization of replicative DNA helicases before and after loading onto DNA has been studied in bacteria and viruses but not eukaryotes and is of major ..
  40. pmc Reconstitution of DNA repair synthesis in vitro and the role of polymerase and helicase activities
    Marek Sebesta
    Department of Biology, Masaryk University, Kamenice 5 A7, 625 00 Brno, Czech Republic
    DNA Repair (Amst) 10:567-76. 2011
    ..The experimental system described here can be employed to increase our understanding of HR events following D-loop formation, as well as the regulatory mechanisms involved...
  41. pmc The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo
    Cyril Ribeyre
    Recombinaison et Instabilité Génétique, Institut Curie Centre de Recherche, CNRS UMR3244, Universite Pierre et Marie Curie, Paris, France
    PLoS Genet 5:e1000475. 2009
    ..Inactivation of other DNA helicases, including Sgs1, had no effect on CEB1 stability...
  42. pmc SMARCAL1 catalyzes fork regression and Holliday junction migration to maintain genome stability during DNA replication
    Remy Betous
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Genes Dev 26:151-62. 2012
    ..If damage is present, it remodels the fork to promote repair and restart. Failures in the process lead to activation of an alternative repair mechanism that depends on MUS81-catalyzed cleavage of the damaged fork...
  43. ncbi Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits
    M L Phelan
    Department of Molecular Biology, Massachusetts General Hospital, Boston 02114, USA
    Mol Cell 3:247-53. 1999
    ..The addition of INI1, BAF155, and BAF170 to BRG1 increases remodeling activity to a level comparable to that of the whole hSWI/SNF complex. These data define the functional core of the hSWI/SNF complex...
  44. pmc Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae
    F Pâques
    Rosenstiel Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02454 9110, USA
    Microbiol Mol Biol Rev 63:349-404. 1999
    ..This review encompasses these different aspects of DSB-induced recombination in Saccharomyces and attempts to relate genetic, molecular biological, and biochemical studies of the processes of DNA repair and recombination...
  45. pmc Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends
    Zhu Zhu
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Cell 134:981-94. 2008
    ..These results provide important insights into the early steps of DSB repair in eukaryotes...
  46. ncbi NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities
    Y Xue
    Laboratory of Genetics, National Institute on Aging, National Institute of Health, Gerontology Research Center, Baltimore, Maryland 21224, USA
    Mol Cell 2:851-61. 1998
    ..These results suggest that ATP-dependent chromatin remodeling can participate in transcriptional repression by assisting repressors in gaining access to chromatin...
  47. pmc Mycobacteria exploit three genetically distinct DNA double-strand break repair pathways
    Richa Gupta
    Immunology Program Molecular Biology Program, Sloan Kettering Institute, New York, NY 10065, USA
    Mol Microbiol 79:316-30. 2011
    ..These findings reveal distinctive features of mycobacterial DSB repair, most notably the dedication of the RecBCD and AdnAB helicase-nuclease machines to distinct repair pathways...
  48. 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
    ..The mechanism presented is pertinent to understanding how other receptors specifically recognize Ub- and Ubl-modified substrates to facilitate signal transduction...
  49. ncbi FANCM connects the genome instability disorders Bloom's Syndrome and Fanconi Anemia
    Andrew J Deans
    London Research Institute, Cancer Research UK, South Mimms, UK
    Mol Cell 36:943-53. 2009
    ..Moreover, a common phenotype of BS and FA cells-an elevated frequency of sister chromatid exchanges-was due to a loss of interaction of the two complexes through FANCM...
  50. pmc Yeast Rad5 protein required for postreplication repair has a DNA helicase activity specific for replication fork regression
    Andras Blastyak
    Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Temesvari krt 62, H 6726, Hungary
    Mol Cell 28:167-75. 2007
    ..These observations provide insight into the mechanism of postreplicational repair in which Rad5 action promotes template switching for error-free damage bypass...
  51. ncbi The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks
    Katsuhiro Hanada
    Department of Cell Biology and Genetics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
    Nat Struct Mol Biol 14:1096-104. 2007
    ..We suggest that Mus81 suppresses chromosomal instability by converting potentially detrimental replication-associated DNA structures into intermediates that are more amenable to DNA repair...
  52. pmc Purification and biochemical heterogeneity of the mammalian SWI-SNF complex
    W Wang
    Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, CA 94305 5428, USA
    EMBO J 15:5370-82. 1996
    ..Certain cell lines completely lack BRG1 and hbrm, indicating that they are not essential for cell viability and that the mammalian SWI-SNF complex may be tailored to the needs of a differentiated cell type...
  53. ncbi Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM
    Alberto Ciccia
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK
    Mol Cell 25:331-43. 2007
    ..Our data indicate that the FANCM/FAAP24 complex may play a key role in recruitment of the FA core complex to damaged DNA...
  54. ncbi Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex
    J K Tong
    Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Nature 395:917-21. 1998
    ..Our results establish a physical and functional link between the distinct chromatin-modifying activities of histone deacetylases and nucleosome remodelling proteins...
  55. ncbi Homologous recombination restarts blocked replication forks at the expense of genome rearrangements by template exchange
    Sarah Lambert
    Institut Curie Centre National de la Recherche Scientifique, UMR3348, Réponse Cellulaire aux Perturbations de la Réplication, Universite Paris Sud XI, Orsay, France
    Mol Cell 39:346-59. 2010
    ..In contrast, we report that the Srs2 helicase promotes both fork restart and template exchange. Our data demonstrate that template exchange occurs during recombination-dependent fork restart at the expense of genome rearrangements...
  56. 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
    ..These findings suggest that dormant origins constitute a major pathway for stalled fork recovery, contributing to faithful chromosome segregation and tumor suppression...
  57. ncbi RTEL-1 enforces meiotic crossover interference and homeostasis
    Jillian L Youds
    DNA Damage Response Laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms, EN6 3LD, UK
    Science 327:1254-8. 2010
    ..Two distinct classes of meiotic COs are increased in rtel-1 mutants, and COI and homeostasis are compromised. We propose that RTEL-1 implements the second level of CO control by promoting noncrossovers...
  58. ncbi Eukaryotic DNA replication control: lock and load, then fire
    Dirk Remus
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, UK
    Curr Opin Cell Biol 21:771-7. 2009
    The initiation of chromosomal DNA replication involves initiator proteins that recruit and load hexameric DNA helicases at replication origins. This helicase loading step is tightly regulated in bacteria and eukaryotes...
  59. ncbi A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes
    S Bultman
    Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA
    Mol Cell 6:1287-95. 2000
    ..In addition, Brg1 heterozygotes are predisposed to exencephaly and tumors. These results provide evidence that biochemically similar chromatin-remodeling complexes have dramatically different functions during mammalian development...
  60. pmc Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler
    Aaron J Gottschalk
    The Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA
    Proc Natl Acad Sci U S A 106:13770-4. 2009
    ..We propose that poly(ADP-ribosyl)ation of chromatin-associated Parp1 serves as a mechanism for targeting a SNF2 family remodeler to chromatin...
  61. ncbi Diversity and specialization of mammalian SWI/SNF complexes
    W Wang
    Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, California 94305 5428, USA
    Genes Dev 10:2117-30. 1996
    ..However, the complexes in mammals are more diverse than the SWI/SNF complex in yeast and are likely dedicated to developmentally distinct functions...
  62. pmc DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2
    Petr Cejka
    Department of Microbiology, University of California, Davis, Davis, California 95616 8665, USA
    Nature 467:112-6. 2010
    ..We suggest that Top3-Rmi1 and MRX are important for recruitment of the Sgs1-Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes...
  63. pmc The FANCM ortholog Fml1 promotes recombination at stalled replication forks and limits crossing over during DNA double-strand break repair
    Weili Sun
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Mol Cell 32:118-28. 2008
    ..In vitro Fml1 catalyzes both replication fork reversal and D loop disruption, indicating possible mechanisms by which it can fulfill its pro- and antirecombinogenic roles...
  64. pmc RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability
    Dongyi Xu
    Laboratory of Genetics, National Institute on Aging, National Institutes of Health, NIH Biomedical Research Center, Baltimore, Maryland 21224, USA
    Genes Dev 22:2843-55. 2008
    ..Our data suggest that multi-OB-fold complexes mediate two modes of BLM action: via RPA-mediated protein-DNA interaction, and via RMI-mediated protein-protein interactions...
  65. pmc Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae
    Anna Azvolinsky
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Mol Cell 34:722-34. 2009
    ..ORFs of highly transcribed RNA polymerase II genes are a class of natural pause sites that are not exacerbated in rrm3 cells...
  66. ncbi The Mcm2-7 complex has in vitro helicase activity
    Matthew L Bochman
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Mol Cell 31:287-93. 2008
    ..Our results show that purified Mcm2-7 acts as a helicase, provides functional evidence of a Mcm2/5 gate, and lays the foundation for future mechanistic studies of this critical factor...
  67. 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...
  68. pmc Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae
    Hengyao Niu
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 467:108-11. 2010
    ..The resection process involves redundant pathways consisting of nucleases, DNA helicases and associated proteins...
  69. ncbi SWI/SNF-Brg1 regulates self-renewal and occupies core pluripotency-related genes in embryonic stem cells
    Benjamin L Kidder
    EMD Serono Research Institute, Inc, Rockland, Massachusetts, USA
    Stem Cells 27:317-28. 2009
    ..Moreover, Brg1 co-occupied a subset of Oct4, Sox2, Nanog, and PcG protein target genes. These results demonstrate an important role for Brg1 in regulating self-renewal and pluripotency in ES cells...
  70. pmc SLX-1 is required for maintaining genomic integrity and promoting meiotic noncrossovers in the Caenorhabditis elegans germline
    Takamune T Saito
    Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Genet 8:e1002888. 2012
    ..Moreover, we hypothesize that SLX-1 regulates the crossover landscape during meiosis by acting as a noncrossover-promoting factor in a subset of DSBs...
  71. pmc CHD7 cooperates with PBAF to control multipotent neural crest formation
    Ruchi Bajpai
    Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 463:958-62. 2010
    ....
  72. ncbi A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis
    Y Gao
    Howard Hughes Medical Institute, The Children s Hospital, Department of Genetics, Harvard University Medical School, Boston, Massachusetts 02115, USA
    Cell 95:891-902. 1998
    ..Our findings demonstrate that differentiating lymphocytes and neurons strictly require the XRCC4 and DNA ligase IV end-joining proteins and point to the general stage of neuronal development in which these proteins are necessary...
  73. pmc Evolution of the SNF2 family of proteins: subfamilies with distinct sequences and functions
    J A Eisen
    Department of Biological Sciences, Stanford University, CA 94305 5020, USA
    Nucleic Acids Res 23:2715-23. 1995
    ..We discuss possible implications of this evolutionary analysis on the general properties and evolution of the SNF2 family...
  74. pmc Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates
    Li Zheng
    Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA
    Mol Cell 32:325-36. 2008
    ..Taken together, our studies illustrate an evolutionarily diversified role of hDNA2 in mitochondrial DNA replication and repair in a mammalian system...
  75. pmc The Bloom's syndrome gene product promotes branch migration of holliday junctions
    J K Karow
    Imperial Cancer Research Fund Laboratories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom
    Proc Natl Acad Sci U S A 97:6504-8. 2000
    ..The gene mutated in BS, BLM, encodes a member of the RecQ family of DExH box DNA helicases, which also includes the Werner's syndrome gene product...
  76. ncbi Non-hexameric DNA helicases and translocases: mechanisms and regulation
    Timothy M Lohman
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Rev Mol Cell Biol 9:391-401. 2008
    ..For some of these enzymes, self assembly and/or interactions with accessory proteins seem to regulate their translocase and helicase activities...
  77. pmc Co-directional replication-transcription conflicts lead to replication restart
    Houra Merrikh
    Department of Biology, M I T, Cambridge, Massachusetts 02139, USA
    Nature 470:554-7. 2011
    ....
  78. pmc Chl1p, a DNA helicase-like protein in budding yeast, functions in sister-chromatid cohesion
    Robert V Skibbens
    Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania 18015, USA
    Genetics 166:33-42. 2004
    ..b>DNA helicases precede the DNA replication fork and thus will first encounter chromatin sites destined for cohesion...
  79. pmc Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks
    Eun Yong Shim
    Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
    EMBO J 29:3370-80. 2010
    ..However, Mre11 nuclease activity is essential for resection in the absence of extensive resection enzymes. The results provide new insights into how MRX catalyses end resection and recombination initiation...
  80. ncbi The FANCM family of DNA helicases/translocases
    Matthew C Whitby
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom
    DNA Repair (Amst) 9:224-36. 2010
    ..This review summarises our current understanding of the biochemical activities and biological functions of the FANCM family...
  81. ncbi CSB is a component of RNA pol I transcription
    John Bradsher
    Institut de Genetique et de Biologie Moleculaire et Cellulaire CNRS INSERM ULP, F 67404, Illkirch Cedex, France
    Mol Cell 10:819-29. 2002
    ..In addition to revealing an unanticipated function for CSB in rRNA synthesis, we show that the fragility of this complex could be one factor contributing to the CS phenotype...
  82. pmc BRG1 requirement for long-range interaction of a locus control region with a downstream promoter
    Shin Il Kim
    Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 106:2259-64. 2009
    ....
  83. pmc BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges
    Kok Lung Chan
    Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
    EMBO J 26:3397-409. 2007
    ..We present a model for the action of BLM in ensuring complete sister chromatid decatenation in anaphase...
  84. pmc Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome
    Katsuyoshi Horibata
    Laboratories of Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 1 3 Yamadaoka, Suita, Osaka 565 0871, Japan
    Proc Natl Acad Sci U S A 101:15410-5. 2004
    ..Possible explanations for the discrepancy in the genotype-phenotype relationship in UVs1KO are presented...
  85. ncbi Identification and biochemical characterization of a Werner's syndrome protein complex with Ku70/80 and poly(ADP-ribose) polymerase-1
    Baomin Li
    Departments of Molecular Microbiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Biol Chem 279:13659-67. 2004
    ....
  86. ncbi DNA-dependent ATPase activity of bacterial XPB helicases
    Tapan Biswas
    Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109 1065, USA
    Biochemistry 48:2839-48. 2009
    ..Similarly to eukaryotic XPB, bacterial XPB are ATP-dependent 3' --> 5' DNA helicases. The ATPase activity of these XPB helicases is DNA-dependent, requiring a minimum of 4-nucleotide long single-..
  87. pmc Modulation of nucleotide excision repair by mammalian SWI/SNF chromatin-remodeling complex
    Qun Zhao
    Department of Radiology, The Ohio State University, Columbus, Ohio 43210, USA
    J Biol Chem 284:30424-32. 2009
    ....
  88. ncbi Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1
    Samuel P Rowbotham
    Nuclear Dynamics and Function, Babraham Institute, Cambridge CB22 3AT, UK
    Mol Cell 42:285-96. 2011
    ..Our findings suggest that chromatin remodeling by SMARCAD1 ensures that silenced loci, such as pericentric heterochromatin, are correctly perpetuated...
  89. ncbi Patient mutations alter ATRX targeting to PML nuclear bodies
    Nathalie G Berube
    Molecular Medicine Program, Ottawa Health Research Institute, Ottawa, Ontario, Canada
    Eur J Hum Genet 16:192-201. 2008
    ..Moreover, these findings support the hypothesis that ATRX patient mutations represent functional hypomorphs and suggest that loss of proper targeting to PML-NBs is an important contributor to the pathogenesis of the ATR-X syndrome...
  90. pmc Welcome the family of FANCJ-like helicases to the block of genome stability maintenance proteins
    Y Wu
    Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, NIH Biomedical Research Center, 251 Bayview Blvd, Baltimore, MD 21224, USA
    Cell Mol Life Sci 66:1209-22. 2009
    The FANCJ family of DNA helicases is emerging as an important group of proteins for the prevention of human disease, cancer, and chromosomal instability...
  91. pmc Overcoming natural replication barriers: differential helicase requirements
    Ranjith P Anand
    Department of Biology, Tufts University, Medford, MA 02155, USA
    Nucleic Acids Res 40:1091-105. 2012
    ..Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures...
  92. pmc Biochemical characterization of Warsaw breakage syndrome helicase
    Yuliang Wu
    Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 287:1007-21. 2012
    ..The biochemical results are discussed in light of the known cellular defects associated with ChlR1 deficiency...
  93. pmc DNA replication through hard-to-replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase
    Nasim Sabouri
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    Genes Dev 26:581-93. 2012
    ..Thus, Pfh1 promotes DNA replication and separation of converged replication forks and suppresses DNA damage at hard-to-replicate sites...
  94. pmc Replication fork reversal and the maintenance of genome stability
    John Atkinson
    School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
    Nucleic Acids Res 37:3475-92. 2009
    ..Here, we discuss the contexts in which fork regression might occur, the factors that may promote such a reaction and the possible roles of replication fork unwinding in normal DNA metabolism...
  95. ncbi Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination
    J Essers
    Medical Genetics Center, Department of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands
    Cell 89:195-204. 1997
    ..Thus, mRAD54 is not required for the recombination processes that generate functional immunoglobulin and T cell receptor genes...
  96. ncbi Mechanism of homologous recombination: mediators and helicases take on regulatory functions
    Patrick Sung
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA
    Nat Rev Mol Cell Biol 7:739-50. 2006
    ..b>DNA helicases, such as Bloom's syndrome protein (BLM), regulate HR at several levels, in attenuating unwanted HR events and ..
  97. 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...
  98. pmc RAD54 controls access to the invading 3'-OH end after RAD51-mediated DNA strand invasion in homologous recombination in Saccharomyces cerevisiae
    Xuan Li
    Department of Microbiology, University of California, Davis, CA 95616 8665, USA
    Nucleic Acids Res 37:638-46. 2009
    ....
  99. pmc Xenopus DNA2 is a helicase/nuclease that is found in complexes with replication proteins And-1/Ctf4 and Mcm10 and DSB response proteins Nbs1 and ATM
    Karen E Wawrousek
    Division of Biology, California Institute of Technology, Pasadena, CA, USA
    Cell Cycle 9:1156-66. 2010
    ..The nuclease activity of Mre11 is required, since its inhibition delays both full Dna2 recruitment and resection. Dna2 depletion inhibits but does not block resection, and Chk1 and Chk2 induction occurs in the absence of Dna2...
  100. ncbi Yeast recombination factor Rdh54 functionally interacts with the Rad51 recombinase and catalyzes Rad51 removal from DNA
    Peter Chi
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 281:26268-79. 2006
    ..Rad51 complex formation. The Rdh54 expression and purification procedures described here should facilitate the functional dissection of this DNA recombination/repair factor...
  101. ncbi The NS3 protein of hepatitis C virus induces caspase-8-mediated apoptosis independent of its protease or helicase activities
    Elena A Prikhod'ko
    Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    Virology 329:53-67. 2004
    ..These findings suggest that HCV NS3 promotes caspase-8 induced apoptosis at a pathway site distal to FADD, and that flavivirus NS3 may represent a new class of pro-apoptotic proteins...

Research Grants63

  1. STRUCTURAL STUDIES OF DNA REPLICATION AND REPAIR
    Gabriel Waksman; Fiscal Year: 2003
    ..Such structures will provide information on the mechanism of active unwinding by DNA-helicases and of passive unwinding by helix-destabilizing SSB proteins. ..
  2. DNA REPLICATION AND CHROMOSOME STRUCTURE IN YEAST
    Virginia A Zakian; Fiscal Year: 2013
    ..The four aims concern three members of the Pif1 family of DNA helicases, a virtually ubiquitous eukaryotic helicase family that is named for its prototypical member the S...
  3. Genomic Stability and RecQ DNA Helicases in Yeast
    Steven J Brill; Fiscal Year: 2012
    ..One such disease, Bloom Syndrome, arises from defects in BLM, a member of RecQ family of DNA helicases. BLM acts together with DNA topoisomerase III and a newly-identified subunit, Rmi1, to suppress sister ..
  4. DNA Helicases: Mechanisms and Functions
    Kevin D Raney; Fiscal Year: 2013
    ..This work will provide experimental and conceptual tools to investigate other classes of helicases. ..
  5. Joint Molecule Formation During Recombination
    Neil Hunter; Fiscal Year: 2013
    ..Specific Aim 2. To Determine the Roles of DNA Helicases in Regulating Joint Molecule Metabolism...
  6. Roles of the RecQ Helicases BLM and RECQ5 in Genome Maintenance
    Patrick Sung; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): DNA helicases are ubiquitous and vast in number, serving important roles in various facets of chromosome metabolism, including transcription, DNA replication, and DNA repair...
  7. Development of novel single-molecule approaches for nanoscale study of helicases
    Sanford H Leuba; Fiscal Year: 2010
    ..These instruments will allow studies on not only DNA helicases but also other motor proteins that act on nucleic acids, such as DNA and RNA polymerases, DNA repair and ..
  8. Suppression of translocations by RecQ-like DNA helicases
    KRISTINA HILDEGARD SCHMIDT; Fiscal Year: 2012
    ..with extreme cancer risk, such as Bloom's syndrome and Werner syndrome, are associated with mutations in DNA helicases of the RecQ family...
  9. FASEB SRC on "Helicases and Nucleic Acid Translocases: Structure, Mechanism, Fun
    James L Keck; Fiscal Year: 2011
    ..Most prominently, the RecQ and FancJ families of DNA helicases have direct roles in aging...
  10. Determination of regulatory mechanisms for BLM helicase
    Sagar Sengupta; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): BLM is a member of the RecQ family of DNA helicases. Germline mutations in BLM and other members of the RecQ helicase family, WRN and RECQ4, result in autosomal-recessive disorders, Bloom syndrome (..
  11. Single Molecule Study of Helicase Mechanisms
    Taekjip Ha; Fiscal Year: 2013
    ..Several human genetic disorders have also been linked to mutations in DNA helicases and helicases from human pathogen are being actively pursued as drug target...
  12. Petascale Molecular Dynamics Data Processing System
    Klaus Schulten; Fiscal Year: 2010
    ..University of Illinois at Urbana-Champaign to resolve, in atomic detail, single molecule processes involving DNA helicases, lipoprotein assembly, protein synthesis in the ribosome, muscle force generation and elasticity, voltage-..
  13. Regulation of DNA recombination in Saccharomyces cerevisiae
    GRZEGORZ A IRA; Fiscal Year: 2013
    ..the unique and redundant functions of multiple DNA polymerases recruited to DSBs and determine which DNA helicases and other enzymes specifically promote DNA synthesis during homologous recombination...
  14. Molecular analyses of RECQ1 functions in genome maintenance
    Sudha Sharma; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: RECQ1 belongs to the RecQ family of DNA helicases members of which are associated with rare diseases of premature aging and cancer predisposition in humans...
  15. Investigation of DnaB helicase loading for initiating DNA replication
    VALERIE LYNN O'SHEA; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): DNA helicases are multi-subunit, macromolecular machines that use energy derived from ATP hydrolysis to unwind duplex segments to drive essential cellular processes such as DNA replication, ..
  16. ASSEMBLY AND ACTIVATION OF ENZYME-SSDNA COMPLEXES
    Scott W Morrical; Fiscal Year: 2012
    ..of the T4 UvsX recombinase into presynaptic filaments, and we will study the assembly of two different DNA helicases, Gp41 and Dda, onto ssDNA at replication forks and in recombination intermediates...
  17. Mechanism of the BLM/Sgs1 Helicase Complex
    Steven J Brill; Fiscal Year: 2013
    ..The RecQ family of DNA helicases is a key player in the maintenance of genome stability...
  18. Chromatin and DNA Dynamics
    James T Kadonaga; Fiscal Year: 2013
    ..It is therefore essential to identify and to characterize the enzymes that alter DNA structure. For instance, DNA helicases are a large and diverse group of ATP-driven motor proteins that unwind DNA and participate in a broad range of ..
  19. DNA HELICASES IN RECOMBINATION AND REPAIR
    Hannah L Klein; Fiscal Year: 2010
    ..When the repair mechanisms are defective, mutations and chromosome changes occur. These reveal normally silent mutations, which now drive cells to uncontrolled growth associated with human cancers. ..
  20. HELICASE CATALYZED DNA UNWINDING
    Timothy M Lohman; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): DNA helicases are ATP-dependent molecular motor proteins that unwind duplex DNA to form the single stranded (ss) DNA intermediates required for DNA metabolism and genome maintenance in all organisms...
  21. Structural Biology of XPB and XPD Helicases
    John A Tainer; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Hereditary mutations in the DNA helicases XPB and XPD lead to human diseases with different phenotypes reflecting increased cancers or aging: xeroderma pigmentosum (XP), XP combined with Cockayne ..
  22. Mechanism of the eukaryotic replicative DNA helicase
    Johannes Walter; Fiscal Year: 2013
    ..Prokaryotic replicative DNA helicases generally function as a single hexamer that translocates along one strand and excludes the other strand...
  23. FORMATION AND RESOLUTION OF RECOMBINATION INTERMEDIATES
    Patrick Sung; Fiscal Year: 2013
    ..we will tackle several outstanding questions germane for delineating the multi-faceted roles of the conserved DNA helicases Pif1 and Mph1 in the DNA synthesis step of recombination and recombination pathway choice, respectively...
  24. Biochemical Mechanisms and Function of DNA Helicases
    STEPHEN CHARLES KOWALCZYKOWSKI; Fiscal Year: 2013
    ..Understanding the mechanism and function of these motor proteins is a longstanding goal of this research proposal. ..
  25. Recruitment and activation of DnaB helicase in Escherichia coli DNA replication
    Jon M Kaguni; Fiscal Year: 2013
    ..DnaA protein initiates chromosomal DNA replication by orchestrating a step-wise process that leads to two DNA helicases bound to each parental DNA strand, which is necessary for bidirectional fork movement from the chromosomal ..
  26. Helicases: Structure, Function, & Roles in Human Disease
    STEVEN MATSON; Fiscal Year: 2001
    ..The topics to be included for discussion are: helicase structure; helicase function and mechanism; DNA helicases in DNA replication, DNA helicases in DNA repair and recombination, RNA helicases in transcription, splicing, ..
  27. Integrated molecular diagnostic system for the point-of-care
    Huimin Kong; Fiscal Year: 2012
    ..Biohelix's proprietary technology is called helicase-dependent amplification (HDA). It uses DNA helicases to separate DNA strands during exponential amplification at a constant temperature of 65:C...
  28. Small-molecule inhibitors of the human RECQ1 and Bloom DNA helicases
    Opher Gileadi; Fiscal Year: 2009
    ..It is hoped, that such inhibition will make the cancer cells more sensitive to DNA- damaging agents, thus allowing better treatment options for patients with resistant forms of cancer. ..
  29. Mechanisms of genomic instability in cancer
    Paul Watt; Fiscal Year: 2002
    ..Some key guardians of such genome stability have already been identified from a family of DNA helicases, named after the prototypic member RecQ, a bacterial helicase which is required both for initiating the RecF ..
  30. GENOMIC STABILITY AND AGING IN YEAST
    Steven Brill; Fiscal Year: 2003
    ..Both WRN and SGS1 encode 160 kDa proteins belonging to the RecQ family of DNA helicases. Because WRN and SGS1 are likely to function in identical genetic pathways, a search for mutations that ..
  31. DNA MISMATCH REPAIR IN EUKARYOTES
    Satya Prakash; Fiscal Year: 2003
    ..The other components of mismatch repair, including the 5' yields 3' and 3' yields 5' exonucleases and DNA helicases, will be identified by genetic and biochemical studies; their biochemical activities will be further defined, ..
  32. FUNCTION AND MECHANISM OF DNA TOPOISOMERASE
    Tao Shih Hsieh; Fiscal Year: 2010
    ..Aim 2 is to probe the genetic interactions between recQ4 and fop3a. RecQ4 belongs to a family of DNA helicases with critical functions in recombination/repair, and is responsible for a genome instability disease in humans,..
  33. RecqL4, chromosome instability and cancer predisposition
    Guangbin Luo; Fiscal Year: 2010
    ..RECQL4 encodes one of the five homologues of the RecQ family of DNA helicases in humans...
  34. Single molecule nucleic acid enzymology
    KEVIN RANEY; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): DNA helicases are required for virtually every aspect of DNA metabolism, including replication, repair, recombination and transcription...
  35. MOLECULAR BASIS FOR ACCELERATED AGING IN WERNER SYNDROME
    Anna Szekely; Fiscal Year: 2005
    ..While the encoded Werner protein (WRN) shows significant homology to the RecQ family of DNA helicases, its precise cellular function is poorly understood...
  36. MUTATIONAL ANALYSIS OF E COLI DNA TOPOISOMERASE III
    Russell DiGate; Fiscal Year: 2005
    ..In particular, it is becoming increasingly evident that Topo III-like enzymes interact with DNA helicases and act in the suppression of recombination in both yeast and E. coli. Topo III of E...
  37. Conference on DNA Helicases, Cancer and Aging
    Ian Hickson; Fiscal Year: 2002
    ..aging syndromes in humans indicates that there is an urgent need to integrate studies of the basic biology of DNA helicases with studies of cancer and longevity...
  38. Bioagent Characterization by Iterative Extension
    Richard Hurt; Fiscal Year: 2007
    ..b>DNA helicases separate the extension reaction products from the template molecules, allowing iterative non-exponential ..
  39. BACTERIAL DNA HELICASES: TARGETS FOR NOVEL ANTIBIOTICS
    Marjorie Barnes; Fiscal Year: 2005
    ..In Phase II, we will characterize the mechanism of action of the validated hits in more detail and optimize the most promising of these structures utilizing a rational drug design approach to develop antibacterial lead compounds. ..
  40. ROLE OF MAMMALIAN HELICASES IN DNA REPLICATION
    Christopher Umbricht; Fiscal Year: 1993
    ..b>DNA helicases are known to play a central role in the replication of prokaryotic and viral genomes, and can therefor be ..
  41. Genetic control of mitotic recombination in mice
    Guangbin Luo; Fiscal Year: 2009
    ..by applicant): The long-term objective of this project is to define the roles and mechanisms by which the RecQ DNA helicases regulate mitotic recombination and suppress mitotic crossover...
  42. Mechanism of helicase translocation along ss DNA
    Christopher Fischer; Fiscal Year: 2003
    b>DNA helicases are motor proteins that couple the energy generated through nucleotide binding and hydrolysis to DNA unwinding and translocation...
  43. Speaker Travel to EMS 2004 Annual Meeting
    Leona Samson; Fiscal Year: 2004
    ..to the environment, telomeres and genomic stability, systems biology approaches to environmental exposures, DNA helicases, metal toxicity, recombination and the maintenance of genomic stability, human variation in cancer ..
  44. Student Travel to the Environmental Mutagen Society
    Michael Plewa; Fiscal Year: 2004
    ..to the environment; telomeres and genomic stability; systems biology approaches to environmental exposures; DNA helicases; chromatin and protein modifications that influence DNA repair and mutation; recombination and the maintenance ..
  45. Microbial Production Core Facility
    Wolf Dietrich Heyer; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  46. Enzymatic Differences Among Hepatitis C Virus Genotypes
    David Frick; Fiscal Year: 2007
    ..abstract_text> ..
  47. Porous Biomimetric Nanocontainers
    Taekjip Ha; Fiscal Year: 2007
    ..Furthermore we will use these techniques to make new biological discoveries on the activities of RNA enzymes and helicases. ..
  48. Investigation of xrcc5 Mutant Mice
    EDWARD HASTY; Fiscal Year: 2005
    ..The role of the tumor suppression protein, p53, will be analyzed for its impact on oncogenesis in ku80-mutant mice with specific attention given to mammary tissue in a defined mouse model. ..
  49. MECHANISM OF DNA-PROTEIN INTERACTION IN DNA REPLICATION
    Subhasis Biswas; Fiscal Year: 2002
    ..Biochemical studies of purified helicase A will characterize the nucleotidase and helicase activities of this protein. ..
  50. 2008 Single Molecule Approaches to Biology Gordon Research Conference
    Taekjip Ha; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  51. Hepatitis C VIrus NS3 Helicase Inhibitor Discovery
    David Frick; Fiscal Year: 2008
    ..The goal here is to find chemicals that prevent the virus from replicating in human cells. [unreadable] [unreadable] [unreadable]..
  52. REGULATION OF PAPILLOMAVIRUS DNA REPLICATION
    Michael Lentz; Fiscal Year: 2002
    ..This work will contribute significant new information to the fields of papillomavirus biology and DNA replication, and offer new insights into the unique properties of viral latency. ..
  53. Mechanism of Conjugative DNA Transfer
    STEVEN MATSON; Fiscal Year: 2005
    ..Taken together, the results gained from these experiments will advance our understanding of the mechanism of conjugative DNA transfer and will pave the way for future experiments to look at transfer across the cell membrane. ..
  54. HCV NS3: Biological, Biochemical and Structural Analysis
    KEVIN RANEY; Fiscal Year: 2006
    ..We have found that NS5A binds tightly to RNA and to NS5B. We will now examine possible functional interactions between NS5A, NS3, and NS5B and attempt to solve the crystal structure of NS5A. ..
  55. MECHANISM AND REGULATION OF TRANSCRIPTION INITIATION
    Smita Patel; Fiscal Year: 2006
    ..abstract_text> ..
  56. Biochemical basis of WRN and RecQ helicase function
    DAVID ORREN; Fiscal Year: 2007
    ..Sequence conservation between RecQ helicases also indicates that our findings will be applicable to the functions of other RecQ helicases (including BLM and RECQL4) and their relationships to human health. ..
  57. MECHANISM OF RNA HELICASE ACTIVITY BY DEXH/D PROTEINS
    ANNA PYLE; Fiscal Year: 2008
    ..The results will fundamentally extend our knowledge of helicase mechanism and facilitate the development of new HCV inhibitors. ..
  58. Epigenetic Control of Heterochromatin Formation
    Rabindranath De La Fuente; Fiscal Year: 2010
    ..abstract_text> ..
  59. Enzymatic Mechanisms of DNA Helicases
    Steven W Matson; Fiscal Year: 2010
    b>DNA helicases provide the primary mechanism by which duplex DNA is converted to single-stranded DNA (ssDNA) for use as a template in DNA replication and repair or as a substrate in recombination...
  60. Bacterial Proteins Involved in DNA Repair
    Michael Cox; Fiscal Year: 2007
    ..These experiments will provide new information about critical parts of the pathways leading to replication fork reactivation. The ultimate goal is a complete reconstitution of the pathways with pure enzymes. ..