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. ncbi 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
  2. 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
  3. ncbi 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
  4. ncbi 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
  5. ncbi Expandable DNA repeats and human disease
    Sergei M Mirkin
    Department of Biology, Tufts University, Medford, Massachusetts 02155, USA
    Nature 447:932-40. 2007
  6. ncbi 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
  7. 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
  8. ncbi 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
  9. ncbi 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
  10. ncbi 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

Research Grants

  1. Structural Biochemistry of DNA Dealkylation
    John A Tainer; Fiscal Year: 2010
  2. Genetic Instability & Risk for Esophageal Carcinoma
    Xifeng Wu; Fiscal Year: 2009
  3. Cohort Study of Genetic Susceptibility to Cutaneous Malignant Melanoma
    Jiali Han; Fiscal Year: 2009
  4. Cohort Study of Genetic Susceptibility to Cutaneous Malignant Melanoma
    Jiali Han; Fiscal Year: 2009
  5. Cohort Study of Genetic Susceptibility to Cutaneous Malignant Melanoma
    Jiali Han; Fiscal Year: 2010
  6. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2010
  7. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2009
  8. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2011
  9. MOLECULAR BASIS OF IMMUNOGLOBULIN HEAVY CHAIN SWITCH
    JANET M STAVNEZER; Fiscal Year: 2010
  10. MOLECULAR BASIS OF IMMUNOGLOBULIN HEAVY CHAIN SWITCH
    JANET M STAVNEZER; Fiscal Year: 2010

Detail Information

Publications214 found, 100 shown here

  1. ncbi 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...
  2. 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...
  3. ncbi 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...
  4. ncbi 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)...
  5. 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...
  6. ncbi 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.
  7. 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
    ....
  8. ncbi 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...
  9. ncbi 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...
  10. ncbi 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...
  11. ncbi 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...
  12. ncbi 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...
  13. ncbi Maintaining genome stability at the replication fork
    Dana Branzei
    Fondazione IFOM, Istituto FIRC di Oncologia Molecolare, IFOM IEO Campus, Via Adamello 16, 20139 Milan, Italy
    Nat Rev Mol Cell Biol 11:208-19. 2010
    ..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...
  14. 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...
  15. ncbi 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...
  16. ncbi 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...
  17. ncbi 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 ..
  18. ncbi 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...
  19. ncbi 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...
  20. ncbi 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...
  21. 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
    ....
  22. ncbi The checkpoint response to replication stress
    Dana Branzei
    FIRC Institute of Molecular Oncology Foundation IFOM IEO campus, Via Adamello 16, 20139 Milan, Italy
    DNA Repair (Amst) 8:1038-46. 2009
    ..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...
  23. ncbi 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...
  24. ncbi 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/..
  25. ncbi 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...
  26. ncbi 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...
  27. ncbi 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...
  28. ncbi 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
    ....
  29. ncbi 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...
  30. ncbi 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 ..
  31. ncbi 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...
  32. ncbi 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...
  33. ncbi 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...
  34. ncbi 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...
  35. ncbi 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...
  36. 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...
  37. ncbi 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...
  38. ncbi 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...
  39. 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...
  40. 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...
  41. 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...
  42. ncbi 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
    ....
  43. ncbi DNA damage signaling recruits the Rtt107-Slx4 scaffolds via Dpb11 to mediate replication stress response
    Patrice Y Ohouo
    Graduate Program in Biochemistry, Molecular and Cell Biology, Weill Institute for Cell and Molecular Biology, Cornell University, 339 Weill Hall, Ithaca, New York 14853 7202, USA
    Mol Cell 39:300-6. 2010
    ..Though it has been proposed to promote fork repair, the mechanisms by which Mec1 regulates DNA repair factors remain unclear...
  44. ncbi Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps, and promotes checkpoint activation
    Michele Giannattasio
    Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita degli Studi di Milano, Milano, 20133, Italy
    Mol Cell 40:50-62. 2010
    ..Our work has significant implications for understanding the coordination between repair of DNA lesions and checkpoint pathways to preserve genome stability...
  45. ncbi ATM-independent, high-fidelity nonhomologous end joining predominates in human embryonic stem cells
    Bret R Adams
    Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298, USA
    Aging (Albany NY) 2:582-96. 2010
    ..Altogether, we conclude that NHEJ in hESCs is largely independent of ATM, DNA-PKcs, and PARP but dependent on XRCC4 with repair fidelity several-fold greater than in astrocytes...
  46. ncbi The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage
    Dorthe Helena Larsen
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK 2100 Copenhagen, Denmark
    J Cell Biol 190:731-40. 2010
    In response to ionizing radiation (IR), cells delay cell cycle progression and activate DNA repair. Both processes are vital for genome integrity, but the mechanisms involved in their coordination are not fully understood...
  47. ncbi 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...
  48. ncbi 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...
  49. ncbi 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...
  50. ncbi 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...
  51. ncbi PARP inhibition versus PARP-1 silencing: different outcomes in terms of single-strand break repair and radiation susceptibility
    Camille Godon
    Institut Curie, Centre de Recherche INSERM, U612, Institut Curie, Bât 110 112, Centre Universitaire, F 91405 Orsay, France
    Nucleic Acids Res 36:4454-64. 2008
    ..PARP-1 inhibition and deletion thus have different outcomes in terms of SSBR and radiosensitivity...
  52. ncbi 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, ..
  53. ncbi 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...
  54. ncbi 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...
  55. 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...
  56. ncbi 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 ..
  57. ncbi 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...
  58. ncbi 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...
  59. ncbi 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...
  60. ncbi The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease
    Najib M El-Sayed
    Department of Parasite Genomics, Institute for Genomic Research, Rockville, MD 20850, USA
    Science 309:409-15. 2005
    ..cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA...
  61. ncbi Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair
    Ivan M Munoz
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Mol Cell 35:116-27. 2009
    ..Here we describe the identification of human SLX4, a scaffold for DNA repair nucleases XPF-ERCC1, MUS81-EME1, and SLX1...
  62. 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...
  63. ncbi Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein
    Ryotaro Nishi
    Cellular Physiology Laboratory, RIKEN Discovery Research Institute, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Mol Cell Biol 25:5664-74. 2005
    ..These results reveal a novel vital function for centrin 2 in NER, the potentiation of damage recognition by XPC...
  64. ncbi Cell biology. Guiding ATM to broken DNA
    Robert T Abraham
    Signal Transduction Program, The Burnham Institute, La Jolla, CA 92037, USA
    Science 308:510-1. 2005
  65. ncbi Repair of double-strand DNA breaks by the human nonhomologous DNA end joining pathway: the iterative processing model
    Yunmei Ma
    Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, California, USA
    Cell Cycle 4:1193-200. 2005
    ..Non-homologous DNA end joining (NHEJ) is an optimal DNA repair pathway for dealing with such a diverse set of DNA lesions...
  66. ncbi Good timing in the cell cycle for precise DNA repair by BRCA1
    Stephen T Durant
    Molecular Genetics and Microbiology, Cancer Research and Treatment Center, School of Medicine, University of New Mexico, Albuquerque, New Mexico 87131, USA
    Cell Cycle 4:1216-22. 2005
    ..This model provides an explanation for how BRCA1 promotes accurate DSB repair during various phases of the cell cycle and also accounts for the dual effects that BRCA1 and MRN activity have upon DNA repair and S-phase arrest.
  67. ncbi The vertebrate Hef ortholog is a component of the Fanconi anemia tumor-suppressor pathway
    Georgina Mosedale
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Nat Struct Mol Biol 12:763-71. 2005
    ..This discovery sheds light on the origins, regulation and molecular function of the FA tumor-suppressor pathway in the maintenance of genome stability...
  68. ncbi Role of the Schizosaccharomyces pombe F-Box DNA helicase in processing recombination intermediates
    Takashi Morishita
    Department of Molecular Microbiology, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Mol Cell Biol 25:8074-83. 2005
    ..Focus formation of Fbh1 protein was induced by treatment that damages DNA. Thus, the F-box DNA helicase appears to process toxic recombination intermediates, the formation of which is dependent on the function of Rhp51...
  69. ncbi ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex
    Ji Hoon Lee
    Department of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, 1 University Station, A4800, Austin, TX 78712, USA
    Science 308:551-4. 2005
    ..breaks in mammalian cells by phosphorylating proteins that initiate cell-cycle arrest, apoptosis, and DNA repair. We show that the Mre11-Rad50-Nbs1 (MRN) complex acts as a double-strand break sensor for ATM and recruits ATM ..
  70. ncbi Reduction of nucleosome assembly during new DNA synthesis impairs both major pathways of double-strand break repair
    L Kevin Lewis
    Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA
    Nucleic Acids Res 33:4928-39. 2005
    ..These results demonstrate that defective assembly of nucleosomes during new DNA synthesis compromises each of the known pathways of DSB repair and that the effects can be indirect consequences of changes in silenced chromatin structure...
  71. ncbi The 9-1-1 checkpoint clamp physically interacts with polzeta and is partially required for spontaneous polzeta-dependent mutagenesis in Saccharomyces cerevisiae
    Simone Sabbioneda
    Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita degli Studi di Milano, Milano, Italy 20133
    J Biol Chem 280:38657-65. 2005
    ..These results suggest that, in addition to its checkpoint signaling role, the 9-1-1 clamp may physically regulate Polzeta-dependent mutagenesis by controlling the access of Polzeta to damaged DNA...
  72. ncbi Structure and mechanism for DNA lesion recognition
    Wei Yang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Cell Res 18:184-97. 2008
    A fundamental question in DNA repair is how a lesion is detected when embedded in millions to billions of normal base pairs...
  73. ncbi A novel plant gene essential for meiosis is related to the human CtIP and the yeast COM1/SAE2 gene
    Clemens Uanschou
    Department of Chromosome Biology, Max F Perutz Laboratories, University of Vienna, Vienna, Austria
    EMBO J 26:5061-70. 2007
    ..Interestingly, we identified CtIP, an essential protein interacting with the DNA repair machinery, as the mammalian homologue of Com1/Sae2, with important implications for the molecular role of CtIP.
  74. ncbi Rad54 protein stimulates heteroduplex DNA formation in the synaptic phase of DNA strand exchange via specific interactions with the presynaptic Rad51 nucleoprotein filament
    J A Solinger
    Institute of General Microbiology, University of Bern, Bern, CH-3012, Switzerland
    J Mol Biol 307:1207-21. 2001
    ..We conclude that Rad54 protein acts during the synaptic phase of DNA strand exchange and after the formation of presynaptic Rad51 protein-ssDNA filaments...
  75. ncbi Domains in the XPA protein important in its role as a processivity factor
    Claudine L Bartels
    Department of Pathology and Laboratory Medicine, UMDNJ New Jersey Medical School, Newark, NJ 07103, USA
    Biochem Biophys Res Commun 356:219-25. 2007
    ..Mutations in both the zinc finger motif and the large basic cleft in this domain eliminated the ability of XPA to confer a processive mechanism of action on the endonucleases involved in NER...
  76. ncbi DNA interstrand cross-link repair in Saccharomyces cerevisiae
    Peter Lehoczký
    Department of Molecular Genetics, Cancer Research Institute, Bratislava, Slovak Republic
    FEMS Microbiol Rev 31:109-33. 2007
    DNA interstrand cross-links (ICL) present a formidable challenge to the cellular DNA repair apparatus...
  77. ncbi Genetic dissection of vertebrate 53BP1: a major role in non-homologous end joining of DNA double strand breaks
    Kyoko Nakamura
    Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshidakonoe, Sakyo Ku 606 8501, Japan
    DNA Repair (Amst) 5:741-9. 2006
    ..We conclude that the major role of 53BP1 in supporting survival of DT40 cells that have suffered DNA DSBs is in facilitating repair by NHEJ...
  78. ncbi Postreplicative mismatch repair factors are recruited to Epstein-Barr virus replication compartments
    Tohru Daikoku
    Division of Virology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
    J Biol Chem 281:11422-30. 2006
    ..The MMR factors might function for the repair of mismatches that arise during viral replication or act to inhibit recombination between moderately divergent (homologous) sequences...
  79. ncbi An azoospermic man with a double-strand DNA break-processing deficiency in the spermatocyte nuclei: case report
    R B Sciurano
    Facultad de Medicina, , Buenos Aires, Argentina
    Hum Reprod 21:1194-203. 2006
    ....
  80. ncbi Mammalian Rad9 plays a role in telomere stability, S- and G2-phase-specific cell survival, and homologous recombinational repair
    Raj K Pandita
    Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park Ave, St Louis, MO 63108, USA
    Mol Cell Biol 26:1850-64. 2006
    ..Together, these findings provide evidence of roles for mammalian Rad9 in telomere stability and HR repair as a mechanism for promoting cell survival after IR exposure...
  81. ncbi DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA
    Birgitte Ø Wittschieben
    University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 280:39982-9. 2005
    ..Thus, it has been uncertain how DDB could play a specific role in DNA repair of such damage. We investigated DDB function using highly purified proteins...
  82. ncbi Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae
    Lindsey J Bostelman
    Department of Biology, Denison University, 213 Talbot Hall, Granville, Ohio 43023, USA
    DNA Repair (Amst) 6:383-95. 2007
    ..The overall results indicate the existence of distinct and separable roles of histone H3 lysine-79 methylation in the response to UV damage, potentially serving to coordinate the various repair processes...
  83. ncbi Fanconi anemia protein FANCD2 promotes immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination
    Kazuhiko Yamamoto
    Department of Immunology and Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701 0192, Japan
    Mol Cell Biol 25:34-43. 2005
    Recent studies show overlap between Fanconi anemia (FA) proteins and those involved in DNA repair mediated by homologous recombination (HR). However, the mechanism by which FA proteins affect HR is unclear...
  84. ncbi Defective DNA repair and increased genomic instability in Artemis-deficient murine cells
    Sean Rooney
    Howard Hughes Medical Institute, The Children s Hospital, The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 197:553-65. 2003
    ..Moreover, Artemis functions as a genomic caretaker, most notably in prevention of translocations and telomeric fusions. As Artemis deficiency is compatible with human life, Artemis may also suppress genomic instability in humans...
  85. ncbi DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency
    M O'Driscoll
    Genome Damage and Stability Unit, University of Sussex, Brighton, East Sussex, BN1 9RR, United Kingdom
    Mol Cell 8:1175-85. 2001
    ..An unexpected V(D)J recombination phenotype is observed involving a small decrease in rejoining frequency coupled with elevated imprecision at signal junctions...
  86. ncbi hMutSbeta is required for the recognition and uncoupling of psoralen interstrand cross-links in vitro
    Nianxiang Zhang
    Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
    Mol Cell Biol 22:2388-97. 2002
    ..Thus, a novel pathway for processing ICLs has been identified in mammalian cells which involves components of the mismatch repair and nucleotide excision repair pathways...
  87. ncbi DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination
    Chris Allen
    Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
    Proc Natl Acad Sci U S A 99:3758-63. 2002
    ....
  88. ncbi Identification of a novel non-structural maintenance of chromosomes (SMC) component of the SMC5-SMC6 complex involved in DNA repair
    Yoko Fujioka
    Research and Education Center for Genetic Information, Nara Institute of Science and Technology, 8916 5 Takayama, Ikoma, Nara 630 0101, Japan
    J Biol Chem 277:21585-91. 2002
    ..features of the Schizosaccharomyces pombe SMC6 gene, rad18, which is thought to be involved in recombinational DNA repair. We conclude that Nse1p and the SMC5-SMC6 heterodimer together form a high molecular mass complex that is ..
  89. ncbi A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway
    Maria A Marchetti
    Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 0001, USA
    Proc Natl Acad Sci U S A 99:7472-7. 2002
    ..These results suggest that, in fission yeast, the signal activating the intra-S-phase checkpoint is generated only when replication forks encounter DNA damage...
  90. ncbi An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage
    Timothy P Heffernan
    Department of Pathology and Laboratory Medicine, Center for Environmental Health and Susceptibility, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Mol Cell Biol 22:8552-61. 2002
    ..Taken together, these data suggest that the UVC-induced S checkpoint response of inhibition of replicon initiation is mediated by ATR signaling through Chk-1 and is independent of ATM, Nbs1, and Mre11...
  91. ncbi 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...
  92. ncbi Enhanced genomic instability and defective postreplication repair in RAD18 knockout mouse embryonic stem cells
    Satoshi Tateishi
    Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 862 0976, USA
    Mol Cell Biol 23:474-81. 2003
    ..These results indicate that dysfunction of Rad18 greatly increases both the frequency of homologous as well as illegitimate recombination, and that RAD18 contributes to maintenance of genomic stability through postreplication repair...
  93. ncbi DNA structure dependent checkpoints as regulators of DNA repair
    Antony M Carr
    Genome Damage and Stability Centre, University of Sussex, Falmer, Sussex BN1 9RQ, UK
    DNA Repair (Amst) 1:983-94. 2002
    ..Although some of the early genetic analysis indicated a complex relationship between DNA replication, DNA repair and the checkpoint pathways, it is only now becoming apparent that checkpoint proteins regulate multiple DNA ..
  94. ncbi Molecular biology. Beginning at the end
    Antony M Carr
    Genome Damage and Stability Centre, University of Sussex, Falmer, Sussex BN1 9RQ, UK
    Science 300:1512-3. 2003
  95. ncbi Retention but not recruitment of Crb2 at double-strand breaks requires Rad1 and Rad3 complexes
    Li Lin Du
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Mol Cell Biol 23:6150-8. 2003
    ..results suggest that Crb2 functions at the sites of DNA damage, and its regulated persistent localization at damage sites may be involved in facilitating DNA repair and/or maintaining the checkpoint arrest while DNA repair is under way.
  96. ncbi Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex
    W Hayes McDonald
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:45460-7. 2003
    ..sister-chromatid cohesion (Cohesin: Smc1 & Smc3), chromatin condensation (Condensin: Smc2 & Smc4), and DNA repair (Smc5 & Smc6). The SMC heterodimers do not function alone and must associate with essential non-SMC subunits...
  97. ncbi Fission yeast Rad50 stimulates sister chromatid recombination and links cohesion with repair
    E Hartsuiker
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RR, UK
    EMBO J 20:6660-71. 2001
    ..We speculate that Rad50 interacts with the cohesin complex during S phase to assist repair and possibly re-initiation of replication after replication fork collapse...
  98. ncbi Recruitment of Mec1 and Ddc1 checkpoint proteins to double-strand breaks through distinct mechanisms
    T Kondo
    Division of Biological Science, Graduate School of Science, Nagoya University, CREST, Japan Science and Technology Corporation, Chikusa ku, Nagoya 464 0814, Japan
    Science 294:867-70. 2001
    ..activate checkpoint pathways that arrest cell cycle progression and induce the expression of genes required for DNA repair. In budding yeast, the homothallic switching (HO) endonuclease creates a site-specific double-strand break at ..
  99. ncbi The DNA replication priming protein, PriA, is required for homologous recombination and double-strand break repair
    T Kogoma
    Department of Cell Biology, University of New Mexico Health Sciences Center, Albuquerque 87131, USA
    J Bacteriol 178:1258-64. 1996
    ..These results suggest that PriA-dependent primosome assembly is crucial for both homologous recombination and double-strand break repair and support the proposal that these processes in E. coli involve extensive DNA replication...
  100. ncbi A novel role for the budding yeast RAD9 checkpoint gene in DNA damage-dependent transcription
    A Aboussekhra
    Institut Curie, UMR 144 CNRS, 26 Rue d Ulm, 75231 Paris Cedex 05, France
    EMBO J 15:3912-22. 1996
    Cells respond to DNA damage by arresting cell cycle progression and activating several DNA repair mechanisms. These responses allow damaged DNA to be repaired efficiently, thus ensuring the maintenance of genetic integrity...
  101. ncbi A meiotic recombination checkpoint controlled by mitotic checkpoint genes
    D Lydall
    Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721, USA
    Nature 383:840-3. 1996
    ..Rad17 and Rad24 proteins may contribute directly to formation of an arrest signal by association with single-strand DNA in mitosis and meiosis...

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 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...
  17. 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 ..
  18. 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...
  19. 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...
  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 ..