dna repair

Summary

Summary: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.

Top Publications

  1. pmc The DNA damage response: making it safe to play with knives
    Alberto Ciccia
    Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 40:179-204. 2010
  2. pmc The DNA-damage response in human biology and disease
    Stephen P Jackson
    The Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 461:1071-8. 2009
  3. ncbi ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Shuhei Matsuoka
    Department of Genetics and Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 316:1160-6. 2007
  4. pmc The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway
    Michael R Lieber
    Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, California 90089, USA
    Annu Rev Biochem 79:181-211. 2010
  5. ncbi Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
    Hannah Farmer
    Cancer Research UK Gene Function and Regulation Group, London, UK
    Nature 434:917-21. 2005
  6. ncbi A DNA damage checkpoint response in telomere-initiated senescence
    Fabrizio d'Adda di Fagagna
    1 The Wellcome Trust Cancer Research UK Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QR, UK 2 Present address IFOM FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy
    Nature 426:194-8. 2003
  7. ncbi Genome maintenance mechanisms for preventing cancer
    J H Hoeijmakers
    MGC Department of Cell Biology and Genetics, Centre for Biomedical Genetics, Erasmus University, PO Box 1738, 3000DR Rotterdam, The Netherlands
    Nature 411:366-74. 2001
  8. ncbi Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
    Helen E Bryant
    The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
    Nature 434:913-7. 2005
  9. pmc Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications
    Sophie E Polo
    The Gurdon Institute, Department of Biochemistry, University of Cambridge, Cambridge CB21QN, United Kingdom
    Genes Dev 25:409-33. 2011
  10. pmc 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks
    Samuel F Bunting
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 141:243-54. 2010

Detail Information

Publications261 found, 100 shown here

  1. pmc The DNA damage response: making it safe to play with knives
    Alberto Ciccia
    Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 40:179-204. 2010
    ..This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.
  2. pmc The DNA-damage response in human biology and disease
    Stephen P Jackson
    The Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 461:1071-8. 2009
    ..Our improving understanding of DNA-damage responses is providing new avenues for disease management...
  3. ncbi ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Shuhei Matsuoka
    Department of Genetics and Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 316:1160-6. 2007
    ..This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals...
  4. pmc The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway
    Michael R Lieber
    Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, California 90089, USA
    Annu Rev Biochem 79:181-211. 2010
    ..Therefore, patients lacking normal NHEJ are not only sensitive to ionizing radiation (IR), but also severely immunodeficient...
  5. ncbi Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
    Hannah Farmer
    Cancer Research UK Gene Function and Regulation Group, London, UK
    Nature 434:917-21. 2005
    ..These results illustrate how different pathways cooperate to repair damage, and suggest that the targeted inhibition of particular DNA repair pathways may allow the design of specific and less toxic therapies for cancer.
  6. ncbi A DNA damage checkpoint response in telomere-initiated senescence
    Fabrizio d'Adda di Fagagna
    1 The Wellcome Trust Cancer Research UK Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QR, UK 2 Present address IFOM FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy
    Nature 426:194-8. 2003
    ..These markers include nuclear foci of phosphorylated histone H2AX and their co-localization with DNA repair and DNA damage checkpoint factors such as 53BP1, MDC1 and NBS1...
  7. ncbi Genome maintenance mechanisms for preventing cancer
    J H Hoeijmakers
    MGC Department of Cell Biology and Genetics, Centre for Biomedical Genetics, Erasmus University, PO Box 1738, 3000DR Rotterdam, The Netherlands
    Nature 411:366-74. 2001
    ..This review summarizes the main DNA caretaking systems and their impact on genome stability and carcinogenesis...
  8. ncbi Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
    Helen E Bryant
    The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
    Nature 434:913-7. 2005
    Poly(ADP-ribose) polymerase (PARP1) facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Nevertheless, PARP1-/- mice are viable, fertile and do not develop early onset tumours...
  9. pmc Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications
    Sophie E Polo
    The Gurdon Institute, Department of Biochemistry, University of Cambridge, Cambridge CB21QN, United Kingdom
    Genes Dev 25:409-33. 2011
    ..We review these regulatory mechanisms and discuss their biological significance to the DDR...
  10. pmc 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks
    Samuel F Bunting
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 141:243-54. 2010
    Defective DNA repair by homologous recombination (HR) is thought to be a major contributor to tumorigenesis in individuals carrying Brca1 mutations...
  11. ncbi Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes
    Lee Zou
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 300:1542-8. 2003
    ..Our data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling...
  12. ncbi Cancer genes and the pathways they control
    Bert Vogelstein
    Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, Baltimore, Maryland 21231, USA
    Nat Med 10:789-99. 2004
    ..The purposes of this review are to highlight examples of progress in these areas, indicate where knowledge is scarce and point out fertile grounds for future investigation...
  13. pmc Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis
    Mary Ellen Moynahan
    Developmental Biology Program, New York, New York 10065, USA
    Nat Rev Mol Cell Biol 11:196-207. 2010
    ..Recent advances have provided a clearer understanding of the connections between these proteins and of the key steps of homologous recombination and DNA strand exchange...
  14. doi More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance
    Jiri Lukas
    Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Nat Cell Biol 13:1161-9. 2011
    ..Recent research has provided insights into these issues and suggests that chromatin responses induced by DNA damage are not simply the accumulation of 'nuclear foci' but are mechanisms required to guard genome integrity...
  15. doi SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype
    Chantal Stoepker
    Department of Clinical Genetics, Vrije Universiteit VU Medical Center, Amsterdam, The Netherlands
    Nat Genet 43:138-41. 2011
    ..SLX4, which coordinates three separate endonucleases, was recently recognized as an important regulator of DNA repair. Here we report the first human individuals found to have biallelic mutations in SLX4...
  16. ncbi Genomic instability and aging-like phenotype in the absence of mammalian SIRT6
    Raul Mostoslavsky
    Howard Hughes Medical Institute, The Children s Hospital, CBR Institute for Biomedical Research, Harvard University Medical School, Boston, MA 02115, USA
    Cell 124:315-29. 2006
    ..We conclude that one function of SIRT6 is to promote normal DNA repair, and that SIRT6 loss leads to abnormalities in mice that overlap with aging-associated degenerative processes.
  17. doi ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin
    Aaron A Goodarzi
    Genome Damage and Stability Centre, University of Sussex, East Sussex BN1 9RQ, UK
    Mol Cell 31:167-77. 2008
    ..These data suggest that the importance of ATM signaling for DSB repair increases as the heterochromatic component of a genome expands...
  18. ncbi Poly(ADP-ribose): novel functions for an old molecule
    Valerie Schreiber
    Département Intégrité du Génome de l UMR 7175, Centre National de la Recherche Scientifique, Ecole Superieure de Biotechnologie de Strasbourg, Boulevard S Brant, BP 10413, F 67412 Illkirch cedex, France
    Nat Rev Mol Cell Biol 7:517-28. 2006
    ..These functions include transcriptional regulation, telomere cohesion and mitotic spindle formation during cell division, intracellular trafficking and energy metabolism...
  19. doi Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
    Martin F Lavin
    Radiation Biology and Oncology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia
    Nat Rev Mol Cell Biol 9:759-69. 2008
    ....
  20. doi 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
    ....
  21. doi Maintaining genome stability at the replication fork
    Dana Branzei
    Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM IEO Campus, Via Adamello 16, 20139 Milan, Italy
    Nat Rev Mol Cell Biol 11:208-19. 2010
    ..These mechanisms ensure that the local DNA damage response, which enables replication fork progression and DNA repair in S phase, is coupled with cell cycle transitions...
  22. doi Transcription-coupled DNA repair: two decades of progress and surprises
    Philip C Hanawalt
    Department of Biology, Stanford University, 371 Serra Mall, Stanford, California 94305 5020, USA
    Nat Rev Mol Cell Biol 9:958-70. 2008
    ..Futile cycles of TCR at naturally occurring non-canonical DNA structures might contribute to genomic instability and genetic disease...
  23. pmc DNA interstrand crosslink repair and cancer
    Andrew J Deans
    London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms EN63LD, UK
    Nat Rev Cancer 11:467-80. 2011
    ..Understanding how the FA pathway links nucleases, helicases and other DNA-processing enzymes should lead to more targeted uses of ICL-inducing agents in cancer treatment and could provide novel insights into drug resistance...
  24. ncbi Cisplatin: mode of cytotoxic action and molecular basis of resistance
    Zahid H Siddik
    Department of Experimental Therapeutics, Unit 104, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 4009, USA
    Oncogene 22:7265-79. 2003
    ..The molecular signature defining the resistant phenotype varies between tumors, and the number of resistance mechanisms activated in response to selection pressures dictates the overall extent of cisplatin resistance...
  25. doi MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings
    Mitch McVey
    Department of Biology, Tufts University, 165 Packard Avenue, Medford, MA 02155, USA
    Trends Genet 24:529-38. 2008
    ..We propose a mechanistic model for MMEJ and highlight important questions for future research...
  26. pmc Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells
    Teresa Neumaier
    Institute of Radiation Protection, German Research Center for Environmental Health GmbH, Ingolstadter Landstrasse 1, 85764 Neuherberg, Germany
    Proc Natl Acad Sci U S A 109:443-8. 2012
    ....
  27. pmc DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin
    Burkhard Jakob
    Department of Biophysics, GSI Helmholtz Center for Heavy Ion Research, Planckstrasse 1, 64291 Darmstadt, Germany
    Nucleic Acids Res 39:6489-99. 2011
    ..Finally, we describe a local decondensation of HC at the sites of ion hits, potentially allowing for DSB movement via physical forces...
  28. ncbi Regulation of DNA double-strand break repair pathway choice
    Meena Shrivastav
    Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine and Cancer Center, Albuquerque, NM 87131, USA
    Cell Res 18:134-47. 2008
    ....
  29. ncbi Expandable DNA repeats and human disease
    Sergei M Mirkin
    Department of Biology, Tufts University, Medford, Massachusetts 02155, USA
    Nature 447:932-40. 2007
    ..It is becoming clear that the peculiar structures of repeat-containing transcripts are at the heart of the pathogenesis of these diseases...
  30. pmc Targeting DNA topoisomerase II in cancer chemotherapy
    John L Nitiss
    Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Nat Rev Cancer 9:338-50. 2009
    ..These studies promise refined targeting of TOP2 as an effective anticancer strategy...
  31. pmc XRCC3 promotes homology-directed repair of DNA damage 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 13:2633-8. 1999
    ..These results establish that XRCC3-mediated homologous recombination can reverse DNA damage that would otherwise be mutagenic or lethal...
  32. doi Mutation of the RAD51C gene in a Fanconi anemia-like disorder
    Fiona Vaz
    Department of Medical and Molecular Genetics, King s College London School of Medicine, Guy s Hospital, London, UK
    Nat Genet 42:406-9. 2010
    ..RAD51C is a member of the RAD51-like gene family involved in homologous recombination-mediated DNA repair. The mutation results in loss of RAD51 focus formation in response to DNA damage and in increased cellular ..
  33. doi Assembly and function of DNA double-strand break repair foci in mammalian cells
    Simon Bekker-Jensen
    Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen N, Denmark
    DNA Repair (Amst) 9:1219-28. 2010
    ..Despite such advances, however, our understanding of the biological relevance of such DNA repair foci still remains limited...
  34. pmc Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells
    Anand G Patel
    Department of Molecular Pharmacology and Experimental Therapeutics, Radiation Oncology, and Oncology, Mayo Clinic, Rochester, MN 55905, USA
    Proc Natl Acad Sci U S A 108:3406-11. 2011
    ....
  35. 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.
  36. doi Repeat instability as the basis for human diseases and as a potential target for therapy
    Arturo López Castel
    Program of Genetics and Genome Biology, The Hospital for Sick Children, 101 College Avenue, East Tower 15 312, TMDT Toronto, Ontario, Canada, M5G 1L7
    Nat Rev Mol Cell Biol 11:165-70. 2010
    ....
  37. pmc 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers
    Peter Bouwman
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Nat Struct Mol Biol 17:688-95. 2010
    ..BRCA1-mutated tumors show genomic instability, mainly as a consequence of impaired recombinatorial DNA repair. Here we identify p53-binding protein 1 (53BP1) as an essential factor for sustaining the growth arrest induced ..
  38. ncbi Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
    Shideng Bao
    Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 444:756-60. 2006
    ..glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity...
  39. doi Cyclical DNA methylation of a transcriptionally active promoter
    Raphaël Métivier
    Universite de Rennes I, CNRS, UMR 6026 Equipe SPARTE, IFR 140 GFAS, Campus de Beaulieu, 35042 Rennes Cedex, France
    Nature 452:45-50. 2008
    ..Cyclical changes in the methylation status of promoter CpGs may thus represent a critical event in transcriptional achievement...
  40. ncbi Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis
    Marzena Bienko
    Institute for Biochemistry II, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Science 310:1821-4. 2005
    ..Our results indicate that Ub-binding domains of Y-family polymerases play crucial regulatory roles in TLS...
  41. ncbi gammaH2AX foci analysis for monitoring DNA double-strand break repair: strengths, limitations and optimization
    Markus Lobrich
    Darmstadt University of Technology, Radiation Biology and DNA Repair, Darmstadt, Germany
    Cell Cycle 9:662-9. 2010
    ..We discuss the limitations and benefits of the technique, enabling the procedure to be optimally exploited but not misused...
  42. pmc Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair
    Agata Smogorzewska
    Department of Genetics, Howard Hughes Medical Institute, Center for Genetics and Genomics, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cell 129:289-301. 2007
    ..Mutation in FANCI is responsible for loss of a functional FA pathway in a patient with Fanconi anemia complementation group I...
  43. pmc Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin
    Andrea Kinner
    Institute of Medical Radiation Biology, University of Duisburg Essen Medical School, Hufelandstrasse 55, 45122 Essen, Germany
    Nucleic Acids Res 36:5678-94. 2008
    ..We conclude with a critical analysis of the strengths and weaknesses of the approach and present some interesting applications of the resulting methodology...
  44. pmc CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle
    Maximina H Yun
    Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Nature 459:460-3. 2009
    ....
  45. pmc MicroRNA regulation of DNA repair gene expression in hypoxic stress
    Meredith E Crosby
    Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520 8040, USA
    Cancer Res 69:1221-9. 2009
    ..Bioinformatics analyses suggested that these miRs could regulate factors implicated in DNA repair pathways...
  46. doi DNA repair in mammalian cells : Nucleotide excision repair: variations on versatility
    T Nouspikel
    Institute for Cancer Studies, University of Sheffield, Sheffield, United Kingdom
    Cell Mol Life Sci 66:994-1009. 2009
    Nucleotide excision repair (NER) is one of the most versatile DNA repair systems...
  47. pmc Directed networks reveal genomic barriers and DNA repair bypasses to lateral gene transfer among prokaryotes
    Ovidiu Popa
    Institute of Botany III, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
    Genome Res 21:599-609. 2011
    ..revealed that recipient genomes of distant transfers encode proteins of nonhomologous end-joining (NHEJ; a DNA repair mechanism) far more frequently than the recipient lacking that mechanism...
  48. pmc Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2
    Craig MacKay
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Cell 142:65-76. 2010
    ..Depletion of FAN1 from human cells causes hypersensitivity to ICLs, defects in ICL repair, and genome instability. These data at least partly explain how ubiquitination of FANCD2 promotes DNA repair.
  49. pmc ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair
    Claudia Cosentino
    Genome Stability Unit, Clare Laboratories, London Research Institute, Cancer Research UK, South Mimms, UK
    EMBO J 30:546-55. 2011
    ..These data suggest that ATM protects cells from ROS accumulation by stimulating NADPH production and promoting the synthesis of nucleotides required for the repair of DSBs...
  50. doi SIRT6 promotes DNA repair under stress by activating PARP1
    Zhiyong Mao
    Department of Biology, University of Rochester, Rochester, NY 14627, USA
    Science 332:1443-6. 2011
    ....
  51. pmc A chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage
    Danny M Chou
    Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:18475-80. 2010
    ..and mass spectrometry to uncover proteins that associate with damaged DNA, many of which are involved in DNA repair or nucleolar function...
  52. pmc Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining
    Brandi L Mahaney
    Department of Biochemistry and Molecular Biology and The Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1
    Biochem J 417:639-50. 2009
    ..In the present review, we will discuss our current understanding of the mechanism of NHEJ in mammalian cells and discuss the roles of DNA-PKcs and DNA-PK-mediated phosphorylation in NHEJ...
  53. ncbi Cellular processing of platinum anticancer drugs
    Dong Wang
    Department of Chemistry, Massachusetts Institute of Technology, Room 18 498, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Rev Drug Discov 4:307-20. 2005
    ..those involved in regulating drug uptake, the signalling of DNA damage, cell-cycle checkpoints and arrest, DNA repair and cell death...
  54. doi DNA repair pathways as targets for cancer therapy
    Thomas Helleday
    Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, off Roosevelt Drive, Headington, Oxford, OX3 7DQ, UK
    Nat Rev Cancer 8:193-204. 2008
    b>DNA repair pathways can enable tumour cells to survive DNA damage that is induced by chemotherapeutic treatments; therefore, inhibitors of specific DNA repair pathways might prove efficacious when used in combination with DNA-damaging ..
  55. ncbi DNA double-strand break repair: from mechanistic understanding to cancer treatment
    Thomas Helleday
    Radiation Oncology and Biology, University of Oxford, Oxford OX3 7LJ, UK
    DNA Repair (Amst) 6:923-35. 2007
    ....
  56. doi The influence of heterochromatin on DNA double strand break repair: Getting the strong, silent type to relax
    Aaron A Goodarzi
    Genome Damage and Stability Centre, University of Sussex, East Sussex BN1 9RQ, United Kingdom
    DNA Repair (Amst) 9:1273-82. 2010
    ..Collectively, these recent studies highlight not only how chromatin complexity influences the factors required for DSB repair but also the pathway choice...
  57. pmc Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11
    Katharina Schlacher
    Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 145:529-42. 2011
    ..Thus, BRCA2 prevents rather than repairs nucleolytic lesions at stalled replication forks to maintain genomic integrity and hence likely suppresses tumorigenesis through this replication-specific function...
  58. pmc Human SIRT6 promotes DNA end resection through CtIP deacetylation
    Abderrahmane Kaidi
    Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Science 329:1348-53. 2010
    ..These findings further clarify how SIRT6 promotes genome stability...
  59. pmc Balancing repair and tolerance of DNA damage caused by alkylating agents
    Dragony Fu
    Department of Biological Engineering, Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Rev Cancer 12:104-20. 2012
    ..Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity...
  60. ncbi Oxidative DNA damage: mechanisms, mutation, and disease
    Marcus S Cooke
    Oxidative Stress Group, Department of Clinical Biochemistry, University of Leicester, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, LE2 7LX, UK
    FASEB J 17:1195-214. 2003
    ....
  61. doi A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling
    Cecilia Cotta-Ramusino
    Department of Genetics, Harvard University Medical School, Howard Hughes Medical Institute, Division of Genetics, Brigham and Women s Hospital, Boston, MA 02115, USA
    Science 332:1313-7. 2011
    The DNA damage response (DDR) is brought about by a protein kinase cascade that orchestrates DNA repair through transcriptional and posttranslational mechanisms. Cell cycle arrest is a hallmark of the DDR...
  62. pmc The ancient and evolving roles of cohesin in gene expression and DNA repair
    Dale Dorsett
    Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA
    Curr Biol 22:R240-50. 2012
    ..complex, named for its key role in sister chromatid cohesion, also plays critical roles in gene regulation and DNA repair. It performs all three functions in single cell eukaryotes such as yeasts, and in higher organisms such as man...
  63. pmc Human CtIP mediates cell cycle control of DNA end resection and double strand break repair
    Pablo Huertas
    Gurdon Institute and Department of Zoology, University of Cambridge, Cambridge CB2 1QN, United Kingdom
    J Biol Chem 284:9558-65. 2009
    ..These results suggest that CDK-mediated control of resection in human cells operates by mechanisms similar to those recently established in yeast...
  64. pmc Significance analysis of microarrays applied to the ionizing radiation response
    V G Tusher
    Departments of Medicine and Biochemistry, Stanford University, 269 Campus Drive, Center for Clinical Sciences Research 1115, Stanford, CA 94305-5151, USA
    Proc Natl Acad Sci U S A 98:5116-21. 2001
    ..Surprisingly, four nucleotide excision repair genes were induced, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation...
  65. pmc Purified human BRCA2 stimulates RAD51-mediated recombination
    Ryan B Jensen
    Department of Microbiology, University of California, Davis, California 95616, USA
    Nature 467:678-83. 2010
    ..report the purification of full-length BRCA2 and show that it both binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA)...
  66. ncbi Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery
    Angelo Lombardo
    San Raffaele Telethon Institute for Gene Therapy, Via Olgettina, 58, 20132 Milan, Italy
    Nat Biotechnol 25:1298-306. 2007
    ....
  67. pmc Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA
    Jie Liu
    Department of Microbiology, University of California Davis, Davis, CA, USA
    Nat Struct Mol Biol 17:1260-2. 2010
    ..We report the purification of full-length human BRCA2 and show that it binds to ~6 RAD51 molecules and promotes RAD51 binding to ssDNA coated by replication protein A (RPA), in a manner that is stimulated by DSS1...
  68. pmc Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases
    Samira Fekairi
    Genome Instability and Carcinogenesis UPR3081 CNRS, Conventionné par l Université d Aix Marseille 2, IGC, IMM 31 chemin Joseph Aiguier, 13402 Marseille, France
    Cell 138:78-89. 2009
    Structure-specific endonucleases resolve DNA secondary structures generated during DNA repair and recombination...
  69. doi Increased mutagenesis and unique mutation signature associated with mitotic gene conversion
    Wade M Hicks
    Department of Biology and Rosenstiel Center, Brandeis University, Waltham, MA 02454 9110, USA
    Science 329:82-5. 2010
    ..These observations suggest that increased DSB frequencies in oncogene-activated mammalian cells may also increase the probability of acquiring mutations required for transition to a cancerous state...
  70. doi 53BP1-dependent robust localized KAP-1 phosphorylation is essential for heterochromatic DNA double-strand break repair
    Angela T Noon
    Genome Damage and Stability Centre, University of Sussex, East Sussex, BN1 9RQ, UK
    Nat Cell Biol 12:177-84. 2010
    ..We propose that ionizing-radiation induced foci (IRIF) spatially concentrate ATM activity to promote localized alterations in regions of chromatin otherwise inhibitory to repair...
  71. pmc How the fanconi anemia pathway guards the genome
    George Lucian Moldovan
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Annu Rev Genet 43:223-49. 2009
    ..The Fanconi Anemia pathway is thought to coordinate a complex mechanism that enlists elements of three classic DNA repair pathways, namely homologous recombination, nucleotide excision repair, and mutagenic translesion synthesis, in ..
  72. pmc The NuRD chromatin-remodeling complex regulates signaling and repair of DNA damage
    Godelieve Smeenk
    Department of Toxicogenetics, Leiden University Medical Center, Leiden 2300RC, Netherlands
    J Cell Biol 190:741-9. 2010
    ..IR)-induced DNA double-strand breaks (DSBs) by orchestrating events that coordinate cell cycle progression and DNA repair. How cells signal and repair DSBs is not yet fully understood...
  73. pmc p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage
    H Christian Reinhardt
    Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18 580, Cambridge, MA 02139, USA
    Cancer Cell 11:175-89. 2007
    ..response to DNA damage, eukaryotic cells activate ATM-Chk2 and/or ATR-Chk1 to arrest the cell cycle and initiate DNA repair. We show that, in the absence of p53, cells depend on a third cell-cycle checkpoint pathway involving p38MAPK/..
  74. doi The checkpoint response to replication stress
    Dana Branzei
    FIRC Institute of Molecular Oncology Foundation IFOM IEO campus, Via Adamello 16, 20139 Milan, Italy
    DNA Repair (Amst) 8:1038-46. 2009
    ..checkpoint is to maintain the integrity of the replication forks while facilitating replication completion and DNA repair and coordinating these events with cell cycle transitions...
  75. doi BRCA1 and its toolbox for the maintenance of genome integrity
    Michael S Y Huen
    Department of Anatomy, The University of Hong Kong, Laboratory Block, 21 Sassoon Road, Hong Kong
    Nat Rev Mol Cell Biol 11:138-48. 2010
    ..Thus, BRCA1 is emerging as the master regulator of the genome through its ability to execute and coordinate various aspects of the DNA damage response...
  76. doi Human DNA damage response and repair deficiency syndromes: linking genomic instability and cell cycle checkpoint proficiency
    Claudia Kerzendorfer
    Human DNA Damage Response Disorders Group, Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, East Sussex, BN1 9RQ, UK
    DNA Repair (Amst) 8:1139-52. 2009
    ..Finally, we will discuss how defects in the DDR result in some unexpected clinical features before describing how the nature of a DDR defect impacts on the management and treatment of individuals with these conditions...
  77. doi Identification of Holliday junction resolvases from humans and yeast
    Stephen C Y Ip
    Genetic Recombination Laboratory, Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
    Nature 456:357-61. 2008
    Four-way DNA intermediates, also known as Holliday junctions, are formed during homologous recombination and DNA repair, and their resolution is necessary for proper chromosome segregation...
  78. pmc Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair
    Jennifer M Svendsen
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 138:63-77. 2009
    ..Here, we identify BTBD12 as the human ortholog of the budding yeast DNA repair factor Slx4p and D. melanogaster MUS312...
  79. doi Collaboration and competition between DNA double-strand break repair pathways
    Elizabeth M Kass
    Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    FEBS Lett 584:3703-8. 2010
    ....
  80. pmc Yeast Mph1 helicase dissociates Rad51-made D-loops: implications for crossover control in mitotic recombination
    Rohit Prakash
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Genes Dev 23:67-79. 2009
    ..Importantly, Mph1, but not a helicase-defective variant, dissociates Rad51-made D-loops. Overall, the results from our analyses suggest a new role of Mph1 in promoting the noncrossover repair of DNA double-strand breaks...
  81. pmc Activation of the DNA damage checkpoint in yeast lacking the histone chaperone anti-silencing function 1
    Christopher Josh Ramey
    Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center at Fitzsimons, P O Box 6511, Aurora, CO 80045, USA
    Mol Cell Biol 24:10313-27. 2004
    ..than the failure to repair double-strand DNA breaks, because asf1 mutants are fully functional for double-strand DNA repair. Our data indicate that the altered chromatin structure in asf1 mutants leads to elevated rates of spontaneous ..
  82. pmc Nucleotide excision repair-induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response
    Jurgen A Marteijn
    Department of Genetics, Center for Biomedical Genetics, Erasmus Medical Center, 3015 GE Rotterdam, Netherlands
    J Cell Biol 186:835-47. 2009
    ..Although both lesions are processed by independent repair pathways and trigger signaling responses by distinct kinases, they eventually generate the same epigenetic mark, possibly functioning in DNA damage signal amplification...
  83. pmc Double Holliday junctions are intermediates of DNA break repair
    Malgorzata Bzymek
    Department of Microbiology, University of California Davis, Davis, California 95616, USA
    Nature 464:937-41. 2010
    ..Thus, although DHJs are identified as intermediates of DSB-promoted recombination in both mitotic and meiotic cells, their formation is distinctly regulated according to the specific dictates of the two cellular programs...
  84. pmc Roles of Werner syndrome protein in protection of genome integrity
    Marie L Rossi
    Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA
    DNA Repair (Amst) 9:331-44. 2010
    ..In this work, we will summarize some of the early studies on the cellular roles of WRN and highlight the recent findings that shed some light on the link between the protein with its cellular functions and the disease pathology...
  85. pmc ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2
    Andrea Beucher
    Darmstadt University of Technology, Radiation Biology and DNA Repair, Darmstadt, Germany
    EMBO J 28:3413-27. 2009
    ..We suggest that Artemis endonuclease removes lesions or secondary structures, which inhibit end resection and preclude the completion of HR or NHEJ...
  86. doi The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress
    Joanna R Morris
    Department of Medical and Molecular Genetics, King s College London, Guy s Medical School Campus, London SE1 9RT, UK
    Nature 462:886-90. 2009
    ..These data demonstrate that the SUMOylation pathway plays a significant role in mammalian DNA damage response...
  87. pmc The emerging role of nuclear architecture in DNA repair and genome maintenance
    Tom Misteli
    National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Nat Rev Mol Cell Biol 10:243-54. 2009
    b>DNA repair and maintenance of genome stability are crucial to cellular and organismal function, and defects in these processes have been implicated in cancer and ageing...
  88. ncbi Meganucleases and DNA double-strand break-induced recombination: perspectives for gene therapy
    Frédéric Pâques
    Cellectis SA, 102, route de Noisy, 93 340 Romainville Cedex France
    Curr Gene Ther 7:49-66. 2007
    ..Finally, we will discuss the main issues that will need to be addressed in order to bring this promising technology to the patient...
  89. ncbi The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair
    Claus Storgaard Sørensen
    Danish Cancer Society, Institute of Cancer Biology, DK 2100 Copenhagen, Denmark
    Nat Cell Biol 7:195-201. 2005
    ..After hydroxyurea treatment, the essential recombination repair protein RAD51 is recruited to DNA repair foci performing a vital role in correct HRR...
  90. doi 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...
  91. pmc Role of ATM and the damage response mediator proteins 53BP1 and MDC1 in the maintenance of G(2)/M checkpoint arrest
    Atsushi Shibata
    Genome Damage and Stability Centre, University of Sussex, East Sussex BN1 9RQ, United Kingdom
    Mol Cell Biol 30:3371-83. 2010
    ..The combined repair and checkpoint defects conferred by 53BP1 and MDC1 deficiency act synergistically to enhance chromosome breakage...
  92. pmc A cooperative activation loop among SWI/SNF, gamma-H2AX and H3 acetylation for DNA double-strand break repair
    Han Sae Lee
    Division of Life and Pharmaceutical Sciences, Department of Life Science, Ewha Womans University, Seoul, Republic of Korea
    EMBO J 29:1434-45. 2010
    ..The H3 acetylation on gamma-H2AX nucleosomes is induced by DNA damage. These results collectively suggest that SWI/SNF, gamma-H2AX and H3 acetylation cooperatively act in a feedback activation loop to facilitate DSB repair...
  93. pmc Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair
    Meredith A Morgan
    Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109 5637, USA
    Cancer Res 70:4972-81. 2010
    ..Furthermore, they support the clinical use of AZD7762 in combination with gemcitabine and radiation for patients with locally advanced pancreatic cancer...
  94. pmc SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair
    Ronald A McCord
    Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Aging (Albany NY) 1:109-21. 2009
    ..Together, these findings elucidate a mechanism whereby regulation of dynamic interaction of a DNA repair factor with chromatin impacts on the efficiency of repair, and establish a link between chromatin regulation, ..
  95. pmc Collaborative action of Brca1 and CtIP in elimination of covalent modifications from double-strand breaks to facilitate subsequent break repair
    Kyoko Nakamura
    Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    PLoS Genet 6:e1000828. 2010
    ..We propose that the BRCA1-CtIP complex plays a role in the nuclease-mediated elimination of oligonucleotides covalently bound to polypeptides from DSBs, thereby facilitating subsequent DSB repair...
  96. pmc Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis
    Mary Mohrin
    The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Department of Medicine, Division of Hematology Oncology, University of California San Francisco, San Francisco, CA 94143, USA
    Cell Stem Cell 7:174-85. 2010
    ..We show that quiescent and proliferating HSCs are equally radioprotected but use different types of DNA repair mechanisms...
  97. pmc A structural model for regulation of NHEJ by DNA-PKcs autophosphorylation
    Tracey A Dobbs
    Department of Biochemistry, Southern Alberta Cancer Research Institute, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta T2N 4Z6, Canada
    DNA Repair (Amst) 9:1307-14. 2010
    ....
  98. pmc Stochastic and reversible assembly of a multiprotein DNA repair complex ensures accurate target site recognition and efficient repair
    Martijn S Luijsterburg
    Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands
    J Cell Biol 189:445-63. 2010
    ..assemble and function on chromatin, we combined quantitative analysis of the mammalian nucleotide excision DNA repair (NER) machinery in living cells with computational modeling...
  99. pmc A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability
    Renee D Paulsen
    Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA
    Mol Cell 35:228-39. 2009
    ..These data indicate that preservation of genome stability is mediated by a larger network of biological processes than previously appreciated...
  100. pmc Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA structure-specific endonucleases in DNA repair and recombination
    Sabrina L Andersen
    Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    Mol Cell 35:128-35. 2009
    ..Genetic and biochemical evidence described here and in related papers suggest that MUS312 and BTBD12 direct Holliday junction resolution by at least two distinct endonucleases in different recombination and repair contexts...
  101. pmc miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells
    Ashish Lal
    Immune Disease Institute and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
    Nat Struct Mol Biol 16:492-8. 2009
    ..Therefore, miR-24 upregulation in postreplicative cells reduces H2AX and makes them vulnerable to DNA damage...

Research Grants89

  1. Structural Biochemistry of DNA Dealkylation
    John A Tainer; Fiscal Year: 2010
    ..We propose to characterize the structural cell biology of these two key facets of alkylation damage repair, which are directly relevant to improved cancer chemotherapies and risk assessments for environmental agents. ..
  2. Genetic Instability & Risk for Esophageal Carcinoma
    Xifeng Wu; Fiscal Year: 2009
    ..1.4. Estimate the frequencies of SNPs in DNA repair genes implicated in the NER, BER, and the DSB pathways...
  3. Cohort Study of Genetic Susceptibility to Cutaneous Malignant Melanoma
    Jiali Han; Fiscal Year: 2009
    ..This research will contribute to the scientific basis for identifying individuals at high risk for melanoma and providing individualized risk management strategies. ..
  4. Cohort Study of Genetic Susceptibility to Cutaneous Malignant Melanoma
    Jiali Han; Fiscal Year: 2009
    ..This research will contribute to the scientific basis for identifying individuals at high risk for melanoma and providing individualized risk management strategies. ..
  5. Cohort Study of Genetic Susceptibility to Cutaneous Malignant Melanoma
    Jiali Han; Fiscal Year: 2010
    ..This research will contribute to the scientific basis for identifying individuals at high risk for melanoma and providing individualized risk management strategies. ..
  6. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2010
    ..The goal of this project is to understand the mechanisms of regulation of BER pathway and devise strategies for modulating the expression of BER genes to improve the efficacy of chemopreventives and therapeutics. ..
  7. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2009
    ..The goal of this project is to understand the mechanisms of regulation of BER pathway and devise strategies for modulating the expression of BER genes to improve the efficacy of chemopreventives and therapeutics. ..
  8. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2011
    ..The goal of this project is to understand the mechanisms of regulation of BER pathway and devise strategies for modulating the expression of BER genes to improve the efficacy of chemopreventives and therapeutics. ..
  9. MOLECULAR BASIS OF IMMUNOGLOBULIN HEAVY CHAIN SWITCH
    JANET M STAVNEZER; Fiscal Year: 2010
    ..How these SSBs are then converted to DSBs is less clear. We have reported that another DNA repair pathway, mismatch repair (MMR) is important for this step, and we will investigate its role...
  10. MOLECULAR BASIS OF IMMUNOGLOBULIN HEAVY CHAIN SWITCH
    JANET M STAVNEZER; Fiscal Year: 2010
    ..How these SSBs are then converted to DSBs is less clear. We have reported that another DNA repair pathway, mismatch repair (MMR) is important for this step, and we will investigate its role...
  11. Arsenic-enhanced skin carcinogenesis by UV radiation
    Ke Liu; Fiscal Year: 2009
    ..Although inhibition of DNA repair by arsenite is consistent with the hypothesis that arsenic acts as a co-carcinogen, the actual mechanisms are ..
  12. URACIL/DNA REPAIR IN VITRO AND IN VIVO
    DALE MOSBAUGH; Fiscal Year: 1999
    ..Investigators propose to extend their investigations concerning the mechanism and enzymology of uracil-DNA repair in human and Escherichia coli cells...
  13. Molecular Epidemiology of DNA Repair in Head and Neck Cancer
    Qingyi Wei; Fiscal Year: 2010
    ..We have found an association between increasing risk of SCCHN and suboptimal DNA repair capacity (DRC) that may be determined by adverse genetic variants such as single nucleotide polymorphisms (SNPs) ..
  14. MECHANISMS RESPONSIBLE FOR GENOMIC INSTABILITY IN PREMATURE AGING LAMINOPATHIES
    SUSANA GONZALO HERVAS; Fiscal Year: 2010
    ..Loss of A-type lamins leads to telomere shortening, telomeric chromatin defects, impaired DNA repair, increased genomic instability, and defects in the non-homologous end-joining of dysfunctional telomeres, a ..
  15. DNA REPAIR IN A HORMONE RESPONSIVE GENE
    Michael J Smerdon; Fiscal Year: 2010
    ..Dynamic FRET will be used to monitor the rates of trapping of unwrapped NCPs by DNA repair proteins at site-specific lesions...
  16. DNA REPAIR AND SUSCEPTIBILITY TO ENVIRONMENTAL AGENTS
    Ivan Rusyn; Fiscal Year: 2004
    ..Cells can respond to DNA damage by coordinated induction of DNA repair and it has been shown that differences in the accumulation and removal of DNA lesions in different organs and in ..
  17. DNA REPAIR IN A HORMONE RESPONSIVE GENE
    Michael J Smerdon; Fiscal Year: 2011
    ..Dynamic FRET will be used to monitor the rates of trapping of unwrapped NCPs by DNA repair proteins at site-specific lesions...
  18. Regulation of Nucleotide Excision Repair by Proteolysis
    Pengbo Zhou; Fiscal Year: 2009
    Nucleotide excision repair (NER) is the major DNA repair machinery that removes DNA damage induced by ultraviolet light (UV) and chemical mutagens to prevent genomic instability and tumorigenesis...
  19. Regulation of Nucleotide Excision Repair by Proteolysis
    Pengbo Zhou; Fiscal Year: 2010
    Nucleotide excision repair (NER) is the major DNA repair machinery that removes DNA damage induced by ultraviolet light (UV) and chemical mutagens to prevent genomic instability and tumorigenesis...
  20. Structural Biochemistry of DNA Dealkylation
    John A Tainer; Fiscal Year: 2010
    ..We propose to characterize the structural cell biology of these two key facets of alkylation damage repair, which are directly relevant to improved cancer chemotherapies and risk assessments for environmental agents. ..
  21. RNA Polymerase Transcription Past DNA Adducts
    David A Scicchitano; Fiscal Year: 2011
    ..RNA polymerase behavior during transcription, and to assess the subsequent cellular responses at the level of DNA repair and transcript integrity...
  22. DNA REPAIR IN A HORMONE RESPONSIVE GENE
    Michael Smerdon; Fiscal Year: 1999
    The broad objective of this proposal is to understand the molecular details of transcription-coupled DNA repair, an important defense mechanism against phenotypic changes induced by insults to DNA in mammalian cells...
  23. Structural Biochemistry of DNA Dealkylation
    John Tainer; Fiscal Year: 2009
    ..We propose to characterize the structural cell biology of these two key facets of alkylation damage repair, which are directly relevant to improved cancer chemotherapies and risk assessments for environmental agents. ..
  24. RNA Polymerase Transcription Past DNA Adducts
    David A Scicchitano; Fiscal Year: 2010
    ..RNA polymerase behavior during transcription, and to assess the subsequent cellular responses at the level of DNA repair and transcript integrity...
  25. Structural Biochemistry of DNA Dealkylation
    John Tainer; Fiscal Year: 2009
    ..We propose to characterize the structural cell biology of these two key facets of alkylation damage repair, which are directly relevant to improved cancer chemotherapies and risk assessments for environmental agents. ..
  26. HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGE
    Bruce Demple; Fiscal Year: 2007
    ..Directly test the role of SirtG in DNA repair and the sub-pathways of BER.
  27. Genetic Predictors for DNA Repair Phenotype in CMM
    Qingyi Wei; Fiscal Year: 2007
    ..Our recently completed case-control study provides evidence that low DNA repair for UV-induced DNA damage (as measured by a host-cell reactivation (HCR) assay) may contribute to sporadic CMM ..
  28. DNA Interstrand Crosslinks, Cancer and Aging
    Laura Niedernhofer; Fiscal Year: 2007
    ..The consequences of unrepaired damage are revealed by genetic diseases in which DNA repair pathways are disrupted...
  29. STRUCTURAL STUDIES OF DNA REPAIR PROTEINS
    Tom Ellenberger; Fiscal Year: 2002
    ..Defects in DNA repair have been linked to a growing repair of inherited diseases of humans...
  30. STRUCTURAL BIOCHEMISTRY OF DNA BASE EXCISION REPAIR
    John Tainer; Fiscal Year: 2002
    ..Due to the high sequence homology and functional conservation of DNA repair enzymes, this approach should provide structural information on the basis for enzyme activity and specificity, ..
  31. DNA BASE EXCISION REPAIR IN PLASMODIUM FALCIPARUM
    THEODORE TARASCHI; Fiscal Year: 2005
    ..The replication and control of DNA repair in Plasmodium falciparum are likely to have a number of differences from the mammalian cell...
  32. EXPERIMENTAL FETAL ALCOHOL SYNDROME
    Sandra M Mooney; Fiscal Year: 2010
    ..We will test the hypothesis that developmental exposure to ethanol alters neuronal survival and DNA repair through p53-dependent activities...
  33. COMBATING ALKYLATING AGENT RESISTANCE IN HUMAN GLIOMAS
    JOHN SILBER; Fiscal Year: 2002
    ..The broad, long-term objective is to define the contribution of DNA repair mechanisms to glioma resistance to chemotherapeutic agents (methylating and chloroethylating agents), and to ..
  34. T4 ENDONUCLEASE V--STRUCTURE/FUNCTION ANALYSES
    R Lloyd; Fiscal Year: 1999
    There is a well established link between inefficient DNA repair of ultraviolet (UV) light induced damage and carcinogenesis in man, as demonstrated through the study of the human disease, xeroderma pigmentosum and epidemiological studies ..
  35. Roles of Lig3 and XRCC1 Genes in Genome Stability
    Alan E Tomkinson; Fiscal Year: 2010
    ..Fortunately, a complex network of DNA repair pathways operates to remove DNA lesions...
  36. MODULATING BASE EXCISION REPAIR IN TUMOR DRUG RESISTANCE
    Stanton Gerson; Fiscal Year: 2007
    ..obstacle to effective treatment with alkylating agents in cancer is the presence of elaborate mechanisms of DNA repair. For instance, methylating agents, such as temozolomide (TMZ) form O6-methylguanine (O6/mG), 7-methylguanine (..
  37. Functional Dynamics of Mammalian and Viral DNA Repair Polymerases
    W M BUJALOWSKI; Fiscal Year: 2010
    ..Swine Fever Virus Polymerase X (pol X) provide outstanding model systems to study the molecular mechanism of the DNA repair polymerase action due to its simplified structures and catalytic repertoires...
  38. Skin Cancer Chemoprevention by Silibinin: Mechanisms and Efficacy
    Rajesh Agarwal; Fiscal Year: 2010
    ..SKH-1 hairless mice showed a decrease in UVB-induced CPD formation in skin by silibinin through enhanced DNA repair in a p53-dependent manner...
  39. Functional Dynamics of Mammalian and Viral DNA Repair Polymerases
    W Bujalowski; Fiscal Year: 2007
    ..Swine Fever Virus Polymerase X (pol X) provide outstanding model systems to study the molecular mechanism of the DNA repair polymerase action due to its simplified structures and catalytic repertoires...
  40. Nuclear IRS-1-DNA repair and mutagenesis in medulloblastoma
    Krzysztof Reiss; Fiscal Year: 2010
    ..Our further studies demonstrate that nuclear IRS-1 can inhibit faithful component of DNA repair (homologous recombination DNA repair, HRR) via a direct interaction between IRS-1 and Rad51 detected at the ..