genomic instability


Summary: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.

Top Publications

  1. ncbi An oncogene-induced DNA damage model for cancer development
    Thanos D Halazonetis
    Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH 1205 Geneva, Switzerland
    Science 319:1352-5. 2008
  2. ncbi Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
    Vassilis G Gorgoulis
    Department of Histology and Embryology, School of Medicine, University of Athens, Athens GR 11527, Greece
    Nature 434:907-13. 2005
  3. ncbi DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Nature 434:864-70. 2005
  4. 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
  5. 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
  6. ncbi Genomic instability--an evolving hallmark of cancer
    Simona Negrini
    Department of Molecular Biology, CH 1205 Geneva, Switzerland
    Nat Rev Mol Cell Biol 11:220-8. 2010
  7. pmc The patterns and dynamics of genomic instability in metastatic pancreatic cancer
    Peter J Campbell
    Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 467:1109-13. 2010
  8. 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
  9. ncbi Mitotic catastrophe: a mechanism for avoiding genomic instability
    Ilio Vitale
    Institut National de la Sante et de la Recherche Medicale INSERM, Villejuif, France
    Nat Rev Mol Cell Biol 12:385-92. 2011
  10. ncbi Genome instability: a mechanistic view of its causes and consequences
    Andres Aguilera
    Centro Andaluz de Biologia Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla CSIC, Avd Américo Vespucio s n, 41092 Sevilla, Spain
    Nat Rev Genet 9:204-17. 2008

Detail Information

Publications359 found, 100 shown here

  1. ncbi An oncogene-induced DNA damage model for cancer development
    Thanos D Halazonetis
    Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH 1205 Geneva, Switzerland
    Science 319:1352-5. 2008
    ..This continuous formation of DNA DSBs may contribute to the genomic instability that characterizes the vast majority of human cancers...
  2. ncbi Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
    Vassilis G Gorgoulis
    Department of Histology and Embryology, School of Medicine, University of Athens, Athens GR 11527, Greece
    Nature 434:907-13. 2005
    ..We propose that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations.
  3. ncbi DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Nature 434:864-70. 2005
    ..a genome-wide assessment of allelic imbalances, our data indicate that early in tumorigenesis (before genomic instability and malignant conversion), human cells activate an ATR/ATM-regulated DNA damage response network that ..
  4. 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
    ..Our results illustrate that HR and NHEJ compete to process DNA breaks that arise during DNA replication and that shifting the balance between these pathways can be exploited to selectively protect or kill cells harboring Brca1 mutations...
  5. 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...
  6. ncbi Genomic instability--an evolving hallmark of cancer
    Simona Negrini
    Department of Molecular Biology, CH 1205 Geneva, Switzerland
    Nat Rev Mol Cell Biol 11:220-8. 2010
    b>Genomic instability is a characteristic of most cancers. In hereditary cancers, genomic instability results from mutations in DNA repair genes and drives cancer development, as predicted by the mutator hypothesis...
  7. pmc The patterns and dynamics of genomic instability in metastatic pancreatic cancer
    Peter J Campbell
    Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 467:1109-13. 2010
    ..b>Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent ..
  8. 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
    ..The mechanisms that operate in eukaryotic cells to promote replication fork integrity and coordinate replication with other aspects of chromosome maintenance are becoming clear...
  9. ncbi Mitotic catastrophe: a mechanism for avoiding genomic instability
    Ilio Vitale
    Institut National de la Sante et de la Recherche Medicale INSERM, Villejuif, France
    Nat Rev Mol Cell Biol 12:385-92. 2011
    ..Accordingly, the disruption of mitotic catastrophe precipitates tumorigenesis and cancer progression, and its induction constitutes a therapeutic endpoint...
  10. ncbi Genome instability: a mechanistic view of its causes and consequences
    Andres Aguilera
    Centro Andaluz de Biologia Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla CSIC, Avd Américo Vespucio s n, 41092 Sevilla, Spain
    Nat Rev Genet 9:204-17. 2008
    b>Genomic instability in the form of mutations and chromosome rearrangements is usually associated with pathological disorders, and yet it is also crucial for evolution...
  11. ncbi Chromosome fragile sites
    Sandra G Durkin
    Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109 0618, USA
    Annu Rev Genet 41:169-92. 2007
    ..Their study has merged with that of cell cycle checkpoints and DNA repair, and common fragile sites have provided insight into understanding the consequences of replication stress on DNA damage and genome instability in cancer cells...
  12. ncbi Collisions between replication and transcription complexes cause common fragile site instability at the longest human genes
    Anne Helmrich
    Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS UMR 7104, INSERM U 964, Universite de Strasbourg, BP 10142 67404 Illkirch Cedex, France
    Mol Cell 44:966-77. 2011
    ..Functional replication machinery needs to be involved in the resolution of conflicts between transcription and replication machineries to ensure genomic stability...
  13. 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
  14. 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
    ..We propose that SLX4 acts as a docking platform for multiple structure-specific endonucleases...
  15. 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
    ..that SIRT6 is a nuclear, chromatin-associated protein that promotes resistance to DNA damage and suppresses genomic instability in mouse cells, in association with a role in base excision repair (BER)...
  16. ncbi Common fragile sites: mechanisms of instability revisited
    Michelle Debatisse
    Institut Curie, Centre de Recherche, 26 Rue d Ulm, 75248 Paris, France
    Trends Genet 28:22-32. 2012
    ..These new data reveal the epigenetic nature of CFSs and open the way to a reevaluation of the role played by these sites in the formation of chromosome rearrangements found in tumors from different tissues...
  17. pmc Inhibition of homologous recombination by the PCNA-interacting protein PARI
    George Lucian Moldovan
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Mol Cell 45:75-86. 2012
    Inappropriate homologous recombination (HR) causes genomic instability and cancer...
  18. ncbi 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
  19. 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
  20. pmc Nucleotide deficiency promotes genomic instability in early stages of cancer development
    Assaf C Bester
    Department of Genetics, The Life Sciences Institute, Edmond J Safra Campus, The Hebrew University, Jerusalem, Israel
    Cell 145:435-46. 2011
    ..Our results suggest a model for early oncogenesis in which uncoordinated activation of factors regulating cell proliferation leads to insufficient nucleotides that fail to support normal replication and genome stability...
  21. ncbi Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability
    Robert G Bristow
    Departments of Medical Biophysics and Radiation Oncology, University of Toronto and Ontario Cancer Institute and Princess Margaret Hospital University Health Network, 610 University Avenue, Toronto, Ontario, M5G2M9, Canada
    Nat Rev Cancer 8:180-92. 2008
    ..There are several reasons why this might be, including the capacity of hypoxia to drive genomic instability and alter DNA damage repair pathways...
  22. ncbi Noncanonical mismatch repair as a source of genomic instability in human cells
    Javier Pena-Diaz
    Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Mol Cell 47:669-80. 2012
    ..Importantly, ncMMR is not limited to B cells but occurs also in other cell types. Moreover, it contributes to mutagenesis induced by alkylating agents. Activation of ncMMR may therefore play a role in genomic instability and cancer.
  23. ncbi DNA damage checkpoints: from initiation to recovery or adaptation
    Jiri Bartek
    Department of Cell Cycle and Cancer, and Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Curr Opin Cell Biol 19:238-45. 2007
    ..Such studies highlight the dynamic nature of these processes and help us to better understand the molecular basis, spatiotemporal orchestration and biological significance of the DNA damage response in normal and cancerous cells...
  24. pmc Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency
    Linghua Wang
    Genome Science Division, Research Center for Advanced Science and Technology RCAST, The University of Tokyo, Tokyo 153 8904, Japan
    Genome Res 22:208-19. 2012
    ..Exome-seq revealed intensive genomic instability in a cell line with MLH1 homozygous deletion, indicated by a dramatically elevated rate of somatic ..
  25. ncbi Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease
    Stefan Stein
    Institute for Biomedical Research, Georg Speyer Haus, Frankfurt, Germany
    Nat Med 16:198-204. 2010
    ..Our data show that forced overexpression of EVI1 in human cells disrupts normal centrosome duplication, linking EVI1 activation to the development of genomic instability, monosomy 7 and clonal progression toward myelodysplasia.
  26. 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...
  27. pmc Aneuploidy drives genomic instability in yeast
    Jason M Sheltzer
    David H Koch Institute for Integrative Cancer Research and Howard Hughes Medical Institute HHMI, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 333:1026-30. 2011
    ..extra copies of single chromosomes and found that all aneuploid strains exhibited one or more forms of genomic instability. Most strains displayed increased chromosome loss and mitotic recombination, as well as defective DNA ..
  28. pmc Aberrant chromosome morphology in human cells defective for Holliday junction resolution
    Thomas Wechsler
    London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 471:642-6. 2011
  29. pmc Mus81 and Yen1 promote reciprocal exchange during mitotic recombination to maintain genome integrity in budding yeast
    Chu Kwen Ho
    Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA
    Mol Cell 40:988-1000. 2010
    ..of recombination from reciprocal exchange to BIR results in greatly increased spontaneous loss of heterozygosity (LOH) and chromosome mis-segregation in the mus81Δ yen1Δ mutant, typical of the genomic instability found in tumor cells.
  30. pmc Non-B DNA structure-induced genetic instability and evolution
    Junhua Zhao
    Department of Carcinogenesis, Science Park Research Division, The University of Texas M D Anderson Cancer Center, Smithville, TX 78957, USA
    Cell Mol Life Sci 67:43-62. 2010
    ..of non-B DNA-forming sequences in various species, the classes of genes enriched in non-B DNA-forming sequences, and recent mechanistic studies on DNA structure-induced genomic instability to highlight their importance in genomes.
  31. pmc The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model
    Vahid Ezzatizadeh
    Division of Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, UB8 3PH, UK
    Neurobiol Dis 46:165-71. 2012
    ..These findings reveal substantial differences in the intergenerational dynamics of expanded GAA repeat sequences compared with expanded CAG/CTG repeats, where Msh2 and Msh3 are thought to actively promote repeat expansions...
  32. 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...
  33. pmc ATR: an essential regulator of genome integrity
    Karlene A Cimprich
    Department of Chemical and Systems Biology, Stanford University School of Medicine, Clark Center, 318 Campus Drive, W350B, Stanford, California 94305 5441, USA
    Nat Rev Mol Cell Biol 9:616-27. 2008
  34. ncbi Abundance of ribosomal RNA gene copies maintains genome integrity
    Satoru Ide
    National Institute of Genetics, SOKENDAI, 1111 Yata, Mishima, 411 8540 Japan
    Science 327:693-6. 2010
    ..These results suggest that high concentrations of heavily transcribed genes are toxic to the cells, and therefore amplified genes, such as rDNA, have evolved...
  35. pmc Positional stability of single double-strand breaks in mammalian cells
    Evi Soutoglou
    National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Nat Cell Biol 9:675-82. 2007
    ..with neighbouring chromosomes and loss of local positional constraint correlates with elevated genomic instability. These results support a contact-first model in which chromosome translocations predominantly form among ..
  36. ncbi Diseases of unstable repeat expansion: mechanisms and common principles
    Jennifer R Gatchel
    Department of Neuroscience, Medical Scientist Training Program, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA
    Nat Rev Genet 6:743-55. 2005
    ..In all these diseases, the context of the expanded repeat and the abundance, subcellular localization and interactions of the proteins and RNAs that are affected have key roles in disease-specific phenotypes...
  37. ncbi Tetraploidy, aneuploidy and cancer
    Neil J Ganem
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Curr Opin Genet Dev 17:157-62. 2007
    ..Therefore, abnormal division of tetraploid cells might facilitate genetic changes that lead to aneuploid cancers...
  38. pmc Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells
    Hiroyuki Konishi
    The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 108:17773-8. 2011
    ..Here, we show that heterozygous BRCA1 inactivation results in genomic instability in nontumorigenic human breast epithelial cells in vitro and in vivo...
  39. ncbi Transcription-replication encounters, consequences and genomic instability
    Anne Helmrich
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut National de la Santé et de la Recherche Médicale U 964, Universite de Strasbourg, Illkirch, France
    Nat Struct Mol Biol 20:412-8. 2013
    ..DNA-polymerase complexes may result in clashes of those machineries on the DNA template and thus increase genomic instability. In addition, we summarize strategies evolved in bacteria and eukaryotes to minimize the consequences of ..
  40. 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...
  41. pmc Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability
    Derek C Radisky
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Nature 436:123-7. 2005
    ..stimulate the expression of the transcription factor Snail and EMT, and cause oxidative damage to DNA and genomic instability. These findings identify a previously undescribed pathway in which a component of the breast tumour ..
  42. pmc The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo
    Cyril Ribeyre
    Recombinaison et Instabilité Génétique, Institut Curie Centre de Recherche, CNRS UMR3244, Universite Pierre et Marie Curie, Paris, France
    PLoS Genet 5:e1000475. 2009
    ..Hence, we conclude that CEB1 instability in pif1Delta cells depends on the potential to form G-quadruplex structures, suggesting that Pif1 could play a role in the metabolism of G4-forming sequences...
  43. pmc RTEL1 maintains genomic stability by suppressing homologous recombination
    Louise J Barber
    DNA Damage Response Laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms EN6 3LD, UK
    Cell 135:261-71. 2008
    ..We propose that loss of HR control after deregulation of RTEL1 may be a critical event that drives genome instability and cancer...
  44. pmc Mutation as a stress response and the regulation of evolvability
    Rodrigo S Galhardo
    Department of Molecular and Human Genetics, Baylor College, Houston, Texas 77030 3411, USA
    Crit Rev Biochem Mol Biol 42:399-435. 2007
    ..Growing evidence shows that a variety of environmental stresses induce genomic instability in bacteria, yeast, and human cancer cells, generating occasional fitter mutants and potentially ..
  45. pmc Losing balance: the origin and impact of aneuploidy in cancer
    Andrew J Holland
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093 0670, USA
    EMBO Rep 13:501-14. 2012
    ..We also explore the emerging possibilities for targeting the cause or consequences of aneuploidy therapeutically...
  46. ncbi Preventing replication stress to maintain genome stability: resolving conflicts between replication and transcription
    Rodrigo Bermejo
    Fondazione Istituto FIRC di Oncologia Molecolare, at IFOM IEO Campus Via Adamello 16, 20139 Milan, Italy
    Mol Cell 45:710-8. 2012
    ..The evolutionary implications of such conflicts on genome dynamics and their potential impact on oncogenic stress are discussed...
  47. ncbi Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability
    Xialu Li
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Cell 122:365-78. 2005
    ..Our results support a model by which recruitment of ASF/SF2 to nascent transcripts by RNA polymerase II prevents formation of mutagenic R loop structures...
  48. pmc SUMO-targeted ubiquitin ligases in genome stability
    John Prudden
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    EMBO J 26:4089-101. 2007
    ..Cells lacking Slx8-Rfp accumulate sumoylated proteins, display genomic instability, and are hypersensitive to genotoxic stress...
  49. pmc Replication fork stalling at natural impediments
    Ekaterina V Mirkin
    Department of Biology, Tufts University, Medford, MA 02155, USA
    Microbiol Mol Biol Rev 71:13-35. 2007
    ..This review describes the mechanisms and consequences of replication stalling at various natural impediments, with an emphasis on the role of replication stalling in genomic instability.
  50. ncbi Ploidy and large-scale genomic instability consistently identify basal-like breast carcinomas with BRCA1/2 inactivation
    Tatiana Popova
    Centre de Recherche, University Paris Descartes, Paris, France
    Cancer Res 72:5454-62. 2012
    ..profiled 65 BLC cases using single-nucleotide polymorphism arrays to define a signature of BRCA1-associated genomic instability. Large-scale state transitions (LST), defined as chromosomal break between adjacent regions of at least 10 ..
  51. pmc A pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and intermediate repeats
    Julie van der Zee
    Department of Molecular Genetics, VIB, Antwerp, Belgium
    Hum Mutat 34:363-73. 2013
    ..001) with the most common indel creating one long contiguous imperfect G(4) C(2) repeat, which is likely more prone to replication slippage and pathological expansion...
  52. pmc The Epstein-Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species
    Bettina Gruhne
    Department of Cell and Molecular Biology, Karolinska Institutet, S 17177 Stockholm, Sweden
    Proc Natl Acad Sci U S A 106:2313-8. 2009
    ..These signs of genomic instability are associated with the production of reactive oxygen species (ROS) and are reversed by antioxidants...
  53. pmc R-loop-mediated genomic instability is caused by impairment of replication fork progression
    Wenjian Gan
    College of Life Sciences, Peking University, Beijing 100871, China
    Genes Dev 25:2041-56. 2011
    ..coli and HeLa cells. Our findings thus provide a direct demonstration that R-loop formation impairs DNA replication and that this is responsible for the deleterious effects of R loops on genome stability from bacteria to humans...
  54. pmc Linking RNA polymerase backtracking to genome instability in E. coli
    Dipak Dutta
    Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA
    Cell 146:533-43. 2011
    ..Our results establish RNAP backtracking as the intrinsic hazard to chromosomal integrity and implicate active ribosomes and other anti-backtracking mechanisms in genome maintenance...
  55. pmc Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells
    Gabriel Cuevas-Ramos
    Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1225, F 31076 Toulouse, France
    Proc Natl Acad Sci U S A 107:11537-42. 2010
    ..Therefore, colon colonization with these E. coli strains harboring the pks island could contribute to the development of sporadic colorectal cancer...
  56. pmc CEP152 is a genome maintenance protein disrupted in Seckel syndrome
    Ersan Kalay
    Department of Medical Biology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
    Nat Genet 43:23-6. 2011
    Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage...
  57. pmc Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells
    Ubaldo E Martinez-Outschoorn
    Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, USA
    Cell Cycle 9:3256-76. 2010
    ..We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior...
  58. pmc Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription
    Sandie Tuduri
    Institute of Human Genetics CNRS UPR1142, F 34396 Montpellier, France
    Nat Cell Biol 11:1315-24. 2009
    ..Here, we show that Top1 suppresses genomic instability in mammalian cells by preventing a conflict between transcription and DNA replication...
  59. pmc A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency
    Liu Cao
    Translational Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 35:534-41. 2009
    The molecular pathways leading from genomic instability to cellular senescence and/or cell death remain incompletely characterized...
  60. pmc Yeast Rtt109 promotes genome stability by acetylating histone H3 on lysine 56
    Robert Driscoll
    Wellcome Trust and Cancer Research U K Gurdon Institute and the Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Science 315:649-52. 2007
    ..These data establish Rtt109p as a member of a new class of histone acetyltransferases and show that its actions are critical for cell survival in the presence of DNA damage during S phase...
  61. pmc RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments
    Yiduo Hu
    Department of Genetics, Case Comprehensive Cancer Centre, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio 44106, USA
    Genes Dev 21:3073-84. 2007
    ..Together, our results identify RECQL5 as an important tumor suppressor that may act by preventing inappropriate HR events via Rad51 presynaptic filament disruption...
  62. pmc Disruption of murine Mus81 increases genomic instability and DNA damage sensitivity but does not promote tumorigenesis
    Najoua Dendouga
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Mol Cell Biol 25:7569-79. 2005
    ..Despite these defects, Mus81(-/-) mice do not show increased predisposition to lymphoma or any other malignancy in the first year of life...
  63. ncbi Genomic instability in laminopathy-based premature aging
    Baohua Liu
    Department of Biochemistry, University of Hong Kong, 21 Sassoon Road, Hong Kong
    Nat Med 11:780-5. 2005
    ..Our results indicate that unprocessed prelamin A and truncated lamin A act dominant negatively to perturb DNA damage response and repair, resulting in genomic instability which might contribute to laminopathy-based premature aging.
  64. ncbi The Elg1 replication factor C-like complex functions in PCNA unloading during DNA replication
    Takashi Kubota
    Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK
    Mol Cell 50:273-80. 2013
  65. ncbi MUS81 promotes common fragile site expression
    Songmin Ying
    Weatherall Institute of Molecular Medicine, Department of Oncology, University of Oxford, Oxford OX3 9DS, UK
    Nat Cell Biol 15:1001-7. 2013
    ..Our findings challenge the prevailing view that CFS breakage is a nonspecific process that is detrimental to cells, and indicate that CFS cleavage actually promotes genome stability. ..
  66. pmc Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins
    Huaiyu Sun
    Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    EMBO J 26:4102-12. 2007
    ..Hence, we describe a family of SIM-containing RING-finger proteins that potentially regulates eukaryotic genome stability through linking SUMO-interaction with ubiquitin conjugation...
  67. pmc 53BP1 facilitates long-range DNA end-joining during V(D)J recombination
    Simone Difilippantonio
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 1360, USA
    Nature 456:529-33. 2008
    ..These data suggest a more general role for 53BP1 in maintaining genomic stability during long-range joining of DNA breaks...
  68. pmc TAp73 knockout shows genomic instability with infertility and tumor suppressor functions
    Richard Tomasini
    The Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, Toronto, Ontario M5G 2C1, Canada
    Genes Dev 22:2677-91. 2008
    ..In addition, cells from TAp73(-/-) mice exhibit genomic instability associated with enhanced aneuploidy, which may account for the increased incidence of spontaneous tumors ..
  69. ncbi Radiation-induced transgenerational alterations in genome stability and DNA damage
    R C Barber
    Department of Genetics, University of Leicester, Leicester, Leicestershire, UK
    Oncogene 25:7336-42. 2006
    ..Our data also provide important clues on the still unknown mechanisms of radiation-induced genomic instability.
  70. pmc CtIP Mutations Cause Seckel and Jawad Syndromes
    Per Qvist
    Department of Human Genetics and Department of Biomedicine, Aarhus University, Aarhus, Denmark
    PLoS Genet 7:e1002310. 2011
    ..This work thus identifies CtIP as a disease gene for Seckel and Jawad syndromes and defines a new type of genetic disease mechanism in which a dominant negative mutation yields a recessively inherited disorder...
  71. ncbi Regulation of Myc by miR-34c: A mechanism to prevent genomic instability?
    Ian G Cannell
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, UK
    Cell Cycle 9:2726-30. 2010
    ..In this review we will discuss the emerging role of microRNAs in tumourigenesis with a specific focus on miR-34c-dependent regulation of Myc...
  72. pmc Loss of Rb proteins causes genomic instability in the absence of mitogenic signaling
    Tanja van Harn
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Genes Dev 24:1377-88. 2010
    ..Thus, our results demonstrate that unfavorable growth conditions can cause genomic instability in cells lacking G1/S control...
  73. ncbi The impact of a negligent G2/M checkpoint on genomic instability and cancer induction
    Markus Lobrich
    Darmstadt University of Technology, Radiation Biology and DNA Repair, 64287 Darmstadt, Germany
    Nat Rev Cancer 7:861-9. 2007
    ..Here, we consider the impact of a negligent G2/M checkpoint on genomic stability and cancer risk...
  74. pmc Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype
    Jung Min Kim
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 16:314-20. 2009
    ..Our results indicate that mouse Usp1 functions downstream in the FA pathway. Deubiquitination is a critical event required for Fancd2 nuclear foci assembly, release from chromatin, and function in DNA repair...
  75. pmc Replication stalling at unstable inverted repeats: interplay between DNA hairpins and fork stabilizing proteins
    Irina Voineagu
    Department of Biology, Tufts University, Medford, MA 02155, USA
    Proc Natl Acad Sci U S A 105:9936-41. 2008
    DNA inverted repeats (IRs) are hotspots of genomic instability in both prokaryotes and eukaryotes...
  76. ncbi PCNA, the maestro of the replication fork
    George Lucian Moldovan
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18 82152 Martinsried, Germany
    Cell 129:665-79. 2007
    ..Switching of PCNA partners may be triggered by affinity-driven competition, phosphorylation, proteolysis, and modification of PCNA by ubiquitin and SUMO...
  77. pmc Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation
    Sophia Bornstein
    Department of Otolaryngology, Oregon Health and Science University OHSU, Portland, Oregon, USA
    J Clin Invest 119:3408-19. 2009
    ..Interestingly, both normal head and neck tissue and HNSCC from HN-Smad4-/- mice exhibited increased genomic instability, which correlated with downregulated expression and function of genes encoding proteins in the Fanconi ..
  78. pmc Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice
    Agathi Vassiliki Goula
    Department of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology, UMR 7104 CNRS INSERM UdS, Illkirch, France
    PLoS Genet 5:e1000749. 2009
    ..We propose that the stoichiometry of BER enzymes is one critical factor underlying the tissue selectivity of somatic CAG expansion...
  79. ncbi From polyploidy to aneuploidy, genome instability and cancer
    Zuzana Storchova
    Department of Pediatric Oncology of The Dana Farber Cancer Institute, Children s Hospital and Harvard Medical School, Room M621A, 44 Binney Street Boston, Massachusetts 02115, USA
    Nat Rev Mol Cell Biol 5:45-54. 2004
    ..Genetic instability in these cells might provide a route to aneuploidy and thereby contribute to the development of cancer...
  80. pmc Stem-like cancer cells are inducible by increasing genomic instability in cancer cells
    Yi Liang
    State Key Laboratory of Oncology in Southern China, Guangzhou, China
    J Biol Chem 285:4931-40. 2010
    ..To gain direct evidence that genomic instability is involved in the induction of SLCCs, we utilized multiple approaches to enhance genomic instability and ..
  81. ncbi Genetic alterations and oncogenic pathways associated with breast cancer subtypes
    Xiaolan Hu
    Department of Bioinformatics, Genentech, Inc, South San Francisco, CA, USA
    Mol Cancer Res 7:511-22. 2009 have more frequent loss of phosphatase and tensin homologue and mutation of RB1, which may contribute to genomic instability. We identified and validated seven regions of copy number alteration associated with different subtypes, ..
  82. pmc Identification of a predominant co-regulation among kinetochore genes, prospective regulatory elements, and association with genomic instability
    William C Reinhold
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 6:e25991. 2011
    ..We propose that the comparison of expression profiles in the NCI-60 cell line panel could be a tool for the identification of other gene groups whose products are involved in the assembly of organelle protein complexes...
  83. pmc Upregulation of FOXM1 induces genomic instability in human epidermal keratinocytes
    Muy Teck Teh
    Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AD, UK
    Mol Cancer 9:45. 2010
    ..This indicates that upregulation of FOXM1 may be an early molecular signal required for aberrant cell cycle and cancer initiation...
  84. pmc Bidirectional transcription stimulates expansion and contraction of expanded (CTG)*(CAG) repeats
    Masayuki Nakamori
    Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Hum Mol Genet 20:580-8. 2011
    ..These results suggest that convergent bidirectional transcription, which has been reported at several disease loci, could contribute to somatic instability of highly expanded (CTG)•(CAG) repeats...
  85. ncbi Replication fork dynamics and the DNA damage response
    Rebecca M Jones
    School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
    Biochem J 443:13-26. 2012
    ..If replication fork progression fails to be rescued, this may lead to DNA damage and genomic instability via nuclease processing of aberrant fork structures or incomplete sister chromatid separation during mitosis...
  86. pmc DNA replication stress, genome instability and aging
    William C Burhans
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Nucleic Acids Res 35:7545-56. 2007
    ..In this article, we review evidence that points to DNA replication stress and replication stress-induced genome instability as important factors in aging...
  87. ncbi Single-stranded DNA-binding protein hSSB1 is critical for genomic stability
    Derek J Richard
    Signal Transduction Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia
    Nature 453:677-81. 2008
    ..Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair...
  88. ncbi Fusion tyrosine kinases: a result and cause of genomic instability
    E T P Penserga
    Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA 19140, USA
    Oncogene 26:11-20. 2007
  89. ncbi High-risk but not low-risk HPV E2 proteins bind to the APC activators Cdh1 and Cdc20 and cause genomic instability
    Sophie Bellanger
    Unité Expression Génétique et Maladies, CNRS FRE 2850, Institut Pasteur, Paris, France
    Cell Cycle 4:1608-15. 2005
    ..cells also show polyploidy, chromosomal mis-segregation and centrosome amplification leading to genomic instability. We link these defects to a specific and unusually strong interaction between high-risk E2 and both Cdc20 ..
  90. 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...
  91. pmc DNA end resection by CtIP and exonuclease 1 prevents genomic instability
    Wassim Eid
    Institute of Molecular Cancer Research, University of Zurich, Switzerland
    EMBO Rep 11:962-8. 2010
    ..Thus, our study identifies new functions of CtIP and EXO1 in DNA end resection and provides new information on the regulation of DSB repair pathways, which is a key factor in the maintenance of genome integrity...
  92. pmc Elg1, an alternative subunit of the RFC clamp loader, preferentially interacts with SUMOylated PCNA
    Oren Parnas
    Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv, Israel
    EMBO J 29:2611-22. 2010
    ..Strains carrying mutations in both ELG1 and SRS2 exhibit a synthetic fitness defect that depends on PCNA modification. Our results underscore the importance of Elg1, Srs2 and SUMOylated PCNA in the maintenance of genomic stability...
  93. ncbi CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer
    Daniel J Weisenberger
    Department of Surgery, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90089 9176, USA
    Nat Genet 38:787-93. 2006
    ..Sporadic cases of mismatch repair deficiency occur almost exclusively as a consequence of CIMP-associated methylation of MLH1 . We propose a robust new marker panel to classify CIMP+ tumors...
  94. ncbi Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain
    Peggy F Shelbourne
    Hum Mol Genet 16:1133-42. 2007
  95. ncbi Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA
    Parker L Andersen
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5
    Cell Res 18:162-73. 2008
    ..a collection of mechanisms by which cells survive replication-blocking lesions with or without associated genomic instability. Recent genetic analyses indicate that DDT in eukaryotes, from yeast to human, consists of two parallel ..
  96. ncbi Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability
    Christine Richardson
    Department of Pathology, Institute of Cancer Genetics, Columbia University College of Physicians and Surgeons, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Oncogene 23:546-53. 2004
    b>Genomic instability is characteristic of tumor cells, and a strong correlation exists between abnormal karyotype and tumorigenicity...
  97. pmc BRIT1/MCPH1 is essential for mitotic and meiotic recombination DNA repair and maintaining genomic stability in mice
    Yulong Liang
    The Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
    PLoS Genet 6:e1000826. 2010
    ..and irradiation-induced DNA damages, and its depletion causes a failure in both mitotic and meiotic recombination DNA repair via impairing RAD51/BRCA2's function and as a result leads to infertility and genomic instability in mice.
  98. ncbi The consequences of structural genomic alterations in humans: genomic disorders, genomic instability and cancer
    Rita Colnaghi
    Human DNA Damage Response Disorders Group, Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom
    Semin Cell Dev Biol 22:875-85. 2011
    ..Finally, we will review some of the recent exciting developments surrounding specific CNVs and their contribution to cancer development as well as the latest model for cancer genome rearrangement; 'chromothripsis'...
  99. pmc Combining ATR suppression with oncogenic Ras synergistically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosage-dependent manner
    Oren Gilad
    Abramson Family Cancer Research Institute and Department of Cancer Biology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Cancer Res 70:9693-702. 2010
    ..Here, we show that ATR-Chk1 pathway engagement is essential for limiting genomic instability following oncogenic Ras transformation...
  100. pmc The Caenorhabditis elegans homolog of Gen1/Yen1 resolvases links DNA damage signaling to DNA double-strand break repair
    Aymeric P Bailly
    Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom
    PLoS Genet 6:e1001025. 2010
    ..Our study suggests that GEN-1 might act as a dual function Holliday junction resolvase that may coordinate DNA damage signaling with a late step in DNA double-strand break repair...
  101. pmc Intergenerational and striatal CAG repeat instability in Huntington's disease knock-in mice involve different DNA repair genes
    Ella Dragileva
    Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston MA 02114, USA
    Neurobiol Dis 33:37-47. 2009

Research Grants73

  1. Genetic variation and regulatory networks: Mechanisms and complexity
    DANA PE ER; Fiscal Year: 2009
    ..These tools will be made publicly available, including a friendly graphical user interface and visualization. ..
  2. Optimization of DNA Repair by Abh8
    Lauren Endres; Fiscal Year: 2013 our mouse model will lead to defects in DNA repair and that this will eventually lead to widespread genomic instability and cancer predisposition...
  3. Role of the Y-Located TSPY Gene in Human Oncogenesis
    Yun Fai Chris Lau; Fiscal Year: 2013
    ..The TSPY repeats are hot spots for both genomic instability and epigenetic dysregulation on the Y chromosome...
  4. Bioassay for Breast Cancer Prevention
    JoEllen Welsh; Fiscal Year: 2010
  5. Interplay Between Tissue Architecture and Nuclear Organization in the DNA Damage
    Pierre Alexandre Vidi; Fiscal Year: 2013 sense DSBs, activate repair pathways, and control cell cycle progression to prevent the propagation of genomic instability. A great challenge is to understand the DDR in the context of tissues and to define the influence of the ..
  6. Mouse models of genomic instability and birth defects
    ..Consistent with this function, acd mutant mice have evidence of telomere dysfunction, indicative of genomic instability. While the association between genomic instability and cancer is well documented, the association between ..
    Howard B Lieberman; Fiscal Year: 2013
    ..on basic research and public health where DNA damaging agents are prevalent environmental carcinogens that can induce genomic instability and cancer, and at the same time the work should reveal novel targets for anti-cancer agents.
  8. The Role of MYST Histone Acetyltransferase in Genome Stability
    M Mitchell Smith; Fiscal Year: 2013
    ..Little is known about their range of functions and target pathways. The research proposed in this application is designed to uncover new principles in how these enzymes work, what they do, and how they do it. ..
  9. Folate Status, Genomic Uracil, and the Balance of Base Excision Repair Activity
    Michael D Wyatt; Fiscal Year: 2011
    ..We will investigate the links between BER and folic acid that define the seemingly contradictory pro- and anticancer effects of each. ..
  10. Regulation of Genomic and Epigenomic Stability at CpG Sites
    Alfonso Bellacosa; Fiscal Year: 2013
    ..These studies may lead to novel strategies for the diagnosis and treatment of cancer. ..
  11. Hematopoietic Stem Cells (HSCs) as Juvenile Protective Factors that Alter Aging
    David E Harrison; Fiscal Year: 2011
    ..LT-HSCs, ST-HSCs and CMPs from B6 and BALB mice will be exposed to treatments that cause genomic instability: gamma radiation, DNA polymerase inhibition, and paraquat...
  12. 14th International Workshop on Ataxia-Telangiectasia and ATM
    Richard A Gatti; Fiscal Year: 2010
    ..disorder that is characterized by a progressive cerebellar ataxia, telangiectasia, immunodeficiency, genomic instability, radiation sensitivity, and a markedly increased incidence of cancer, usually lymphoma or leukemia...
  13. Roles of RNA Polymerases IV and V in siRNA-mediated gene silencing
    CRAIG STUART PIKAARD; Fiscal Year: 2013
    ..Our studies of RNA polymerases IV and V are significant with respect to all of these areas, especially the roles of intergenic noncoding RNAs and siRNAs in chromatin-mediated gene silencing. ..
  14. Protein composition and interactions of telemeric chromatin
    Michael P Killoran; Fiscal Year: 2010
    ..Together, a model for telomere breakdown and large-scale approaches for studying chromatin dynamics at telomeres will make a strong contribution to understanding genome instability in cancer formation. ..
  15. Integrating stress MAP kinase signaling with DNA replication origin licensing
    Jeanette Gowen Cook; Fiscal Year: 2013
  16. The role of LKB1 in the maintenance of genomic stability.
    Zhi Xiang Xu; Fiscal Year: 2013
    ..In the last decade, considerable evidence has accumulated suggesting that genomic instability plays an important role in tumorigenesis...
  17. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2012
    ..are crucial for maintaining DNA integrity in normal cells, and defects in the checkpoints may cause genomic instability and ultimately tumorigenesis...
  18. ATM Controls Genomic Stability in Pluripotent Stem Cells
    JASON MARK BECKTA; Fiscal Year: 2013
    ..g., aneuploidy). As these abnormalities can catalyze neoplastic progression, the genomic instability inherent to in vitro work has slowed efforts to bring PSCs from the bench to the bedside...
  19. HTS development for targeted anti-fungal small molecules
    Paul D Kaufman; Fiscal Year: 2010
    ..albicans. We are developing high-throughput screens for compounds that can inhibit this enzyme, because these will be candidates in our search for new anti-fungal drugs. ..
  20. Inactivation of Hdac3 in the cause, prevention, and treatment of HCC
    Scott W Hiebert; Fiscal Year: 2013
    ..Most importantly, consistent with defects in DNA repair and genomic instability, the liver-specific deletion of Hdac3 caused a 100% penetrant hepatocellular carcinoma with a mean time to ..
  21. Metnase, PIKK, and RPA Roles in DNA Damage and Replication Stress Responses
    Jac A Nickoloff; Fiscal Year: 2013
  22. Regulation of KSHV Latency
    Paul M Lieberman; Fiscal Year: 2013
    ..Further elucidation of the molecular mechanisms regulating latency transcription will provide useful information for understanding and treating viral pathogenesis and disease. ..
  23. Roles of the mammalian CST complex in DNA replication and chromosome cohesion
    JASON AARON STEWART; Fiscal Year: 2013
    ..The completion of these studies will advance our understanding of these cellular processes and provide new targets for prevention and treatment of these diseases. ..
  24. Telomere and its bio-regulators as predictors for clinical diabetes in women
    Simin Liu; Fiscal Year: 2010
  25. Chromatin regulation by human SIRT7 in aging-associated cellular programs
    Katrin F Chua; Fiscal Year: 2013
    ..Environmental and metabolic sources of DNA damage and genotoxic stress contribute to genomic instability, aging, and age-related tissue degeneration and pathologies...
  26. Role of Polo-like kinase (Plk-1) in Hepatitis B Virus-mediated Hepatocellular Car
    Ourania M Andrisani; Fiscal Year: 2010
    ..pX-expressing cells with DNA damage escape apoptosis continue to accrue DNA damage and suffer from genomic instability leading to malignant transformation...
    Barbara J Meyer; Fiscal Year: 2013
    ..Thus, studying dosage compensation will help us understand genomic instability caused by errors in chromosome segregation and disruption of meiotic recombination...
  28. Centromere Structure and Function in Candida albicans
    Judith G Berman; Fiscal Year: 2012
    ..We will develop tools to study this process and will identify companion drugs that inhibit these defects, thereby extending the usefulness of available antifungal therapies. ..
  29. Genome instability in leukemia stem cell
    Tomasz Skorski; Fiscal Year: 2010
    ..In the experimental models BCR/ABL kinase promotes ROS-dependent genomic instability, which may lead to resistance to ABL kinase inhibitor imatinib mesylate (IM), and to malignant progression ..
  30. Hyperglycemia-induced DNA damage as a driver of genomic instability
    JOHN S TERMINI; Fiscal Year: 2013
    ..human cells, and that nucleotide excision repair (NER) is the major pathway for minimizing DNA-AGE induced genomic instability. Because NER is downregulated as consequence of adiposity and diabetes we theorize that the accumulation of ..
  31. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2013 of spontaneous and induced alkylation, deamination and peroxidation-induced DNA damage to combat genomic instability and cancer...
  32. Role of FA proteins in hematopoiesis
    Qishen Pang; Fiscal Year: 2013
    ..and vulnerability of chromosomal DNA to oxidative damage would provide a potential genetic mechanism for FA genomic instability, with focus on the roles of FA proteins in oxidative DNA-damage response and repair, and the functional ..
  33. FOXO1 Inhibition in Genotoxic Stress Response and Prostate Cancer Survival
    Haojie Huang; Fiscal Year: 2013
    ..Findings from this study will not only enhance our understanding of age-related prostate cancinogenesis, but could also provide new molecular targets to devise strategies for prostate cancer prevention and therapy. ..
  34. Checkpoints and double strand breaks in S. pombe meiosis
    Susan L Forsburg; Fiscal Year: 2013
    ..This will provide important insights into the stresses that impact meiotic progression in humans as well as yeast. ..
  35. Cytosine DNA Methylation and Transcriptional Repression in African Trypanosomes
    KEVIN MILITELLO; Fiscal Year: 2012
    ..Engineered parasites lacking DNA methylation may over-express surface antigens and serve as a vaccine. ..
  36. CSHL Eukaryotic DNA Replication Conference
    David J Stewart; Fiscal Year: 2013
    ..of tumors, S phase is a major target for chemo- and radiotherapy and errors in DNA replication lead to genomic instability, the relevance of this meeting to cancer research, and ultimately to improved therapies, cannot be ..
    Chi V Dang; Fiscal Year: 2011
    ..that anti- oxidants, such as N-acetylcysteine or vitamin C, decrease tumorigenesis by interfering with genomic instability by squelching reactive oxygen specifes induced by Myc...
  38. Aberrant activation of HGF/MET signaling as a therapeutic target in AML
    Alex Kentsis; Fiscal Year: 2013
    ..whose aberrant activation is widely implicated in carcinogenesis, causing enhanced growth, survival, and genomic instability of cancer cells...
  39. HTLV-I Tax activates the anaphase promoting complex
    Chou Zen Giam; Fiscal Year: 2013
    ..The genomic instability induced by Tax is thought to play an important role in ATLL development...
  40. Role of Beta Spectrin and Smad in Alcohol Induced Liver and GI Cell Proliferation
    Lopa Mishra; Fiscal Year: 2013
    ..c) Expand to fine mapping. Significantly, studies proposed under this application should provide the scientific community with a new understanding of the instrumental regulators in alcohol induced liver injury and neoplasia. ..
  41. Suppression of genomic instability by tuning the DNA damage response at telomeres
    RACHEL L FLYNN; Fiscal Year: 2012
    ..Not surprisingly, critically short or improperly 'capped'telomeres are major sources of genomic instability and have been linked to premature aging, hematological malignancies, and solid tumor formation...
  42. Mitochondrial Roles of the SUV3 in Premature Aging and Cancer
    Wen Hwa Lee; Fiscal Year: 2012
    ..Results derived from these studies will provide a molecular basis to explain how SUV3-mediated RNA degradation plays a role in the aging process and tumorigenesis. ..
  43. Fanconi Anemia as a Model for Susceptibility to Human Papillomavirus Infection
    ..Importantly, our study will positively impact child health now by providing evidence for recommendations for HPV vaccination in individuals with FA. ..
  44. Suppression of genomic instability by tuning the DNA damage response at telomeres
    RACHEL L FLYNN; Fiscal Year: 2013
    ..Not surprisingly, critically short or improperly 'capped'telomeres are major sources of genomic instability and have been linked to premature aging, hematological malignancies, and solid tumor formation...
  45. DNA-PKcs Phosphorylation on Hematopoietic Stem Cells Genome Maintenance
    Benjamin Ping Chi Chen; Fiscal Year: 2013
    ..2. To investigate the effect of DNA-PKcs T2609 cluster phosphorylation on telomere maintenance. 3. To determine the effect of DNA-PKcs T2609 cluster phosphorylation on the production and protection of telomeric 3'overhangs. ..
  46. Analysis of the Human c-myc Gene Replication Origin
    Michael Leffak; Fiscal Year: 2012
    ..We have developed a novel system that mimics the genomic instability observed in cancers and neurodegenerative diseases...
  47. Non-coding RNAs in the epigenetics of human centromere formation
    PETER WARBURTON; Fiscal Year: 2009
    ..These epigenetic marks are currently unknown in human cells, and their discovery will provide great insight into the requirements for centromere formation and function. ..
  48. Development of Novel Agents Targeting Genome Stability and Maintenance for Treati
    John J Turchi; Fiscal Year: 2013
    ..Successful completion of these studies will support a phase II STTR application to pursue Investigational New Drug (IND)-enabling studies, including expanded safety, toxicity, and efficacy studies. ..
    Michel C Nussenzweig; Fiscal Year: 2011
    ..Epub ahead of print] ..
  50. Recombination Repair Complex in Human Cells
    Richard Fishel; Fiscal Year: 2013
  51. Novel histone biotinylation sites and relationships to other epigenetic marks
    JANOS contact ZEMPLENI; Fiscal Year: 2010
    ..Previous studies suggest that biotinylation of histones plays a critical role in the repression of retrotransposons, thereby decreasing the incidence of retrotranspositions, chromosomal abnormalities, and probably cancer risk. ..
  52. Role of Non-Core RAG1 in DSB Repair, Cell Survival, and Cell Cycle Progression
    Julie Horowitz; Fiscal Year: 2013
    ..defects and inability to coordinate DSB repair with cell survival and cell cycle progression result in genomic instability that can cause leukemias and lymphomas...
    Susan K Dutcher; Fiscal Year: 2013
    ..The maturation of centrioles/basal bodies during the cell cycle is likely to play important roles in both asymmetric cell division and signaling. ..
  54. TR4 orphan receptor, a longevity assurance gene, in prostate carcinogenesis
    Yi Fen Lee; Fiscal Year: 2012
    ..Our study will lead to more accurate diagnosis and better prognosis for prostate cancer, and facilitate genetic or pharmacological intervention to slow this disease by utilizing TR4. ..
  55. Plk1-Numb Cooperation in Melanomagenesis
    Nihal Ahmad; Fiscal Year: 2013
    ..cell division and integrity, and loss of Numb and Plk1 regulation deregulates p53 contributing to increased genomic instability and melanomagenesis. We will challenge this hypothesis in three specific aims. ...
  56. Mammalian SIRT6 Is A Master Regulator Of Glucose Homeostasis
    Raul Mostoslavsky; Fiscal Year: 2013
  57. Biomarker Prediction of Gleason Upgrading
    Bruce J Trock; Fiscal Year: 2010
    ..panel is based on the hypothesis that emergence of high-grade prostate cancer is driven by increased genomic instability, global chromatin reorganization and adaptation of cancer cells to hypoxic conditions in the tumor ..
  58. The MRAD9 Radioresistance Gene
    Howard B Lieberman; Fiscal Year: 2013
    The way organisms respond to radiation exposure is important since induced DNA lesions can lead to mutation, genomic instability, and death, cancer or other deleterious health problems...
  59. Regulation of Genomic Instability in Early Breast Cancer
    Thea D Tlsty; Fiscal Year: 2013
    ..abstract_text> ..
  60. Nuclear IRS-1-DNA repair and mutagenesis in medulloblastoma
    Krzysztof Reiss; Fiscal Year: 2012
    ..we have developed a research plan which will analyze fundamental mechanisms leading to the development of genomic instability in medulloblastomas...
  61. Targeted Degradation of DNA Damage Response Proteins by Autophagy
    Thomas J Begley; Fiscal Year: 2013
    ..We will perform genetic, biochemical and proteomic based experiments in S. cerevisiae to test our hypothesis and to define the molecular signals that allow autophagy to target specific proteins for degradation. ..
  62. Genetic Analysis of MSM Protein Function in S. Pombe
    Susan L Forsburg; Fiscal Year: 2012
    ..This project uses genetics and cell biology in a simple yeast to study how these conserved proteins normally work to protect the genome, and to study the molecular consequences when they are disrupted. ..
  63. DNA Repair Capacity and Risk of Pre-malignant Lesion in Lung Epithelium
    Hua Zhao; Fiscal Year: 2009
    ..substantially variable among individuals in the population, and suboptimal DRC of DNA damage might increase genomic instability and hence, increase risk of pre-malignant lesion and eventual lung cancer development...
    Amato Giaccia; Fiscal Year: 1999
    ..viral oncogene products such as the human papillomavirus E6 and E7 proteins are also able to increase genomic instability by reducing or eliminating a G1/S-phase checkpoint through inhibition of p53 and Rb, respectively...
  65. Ciprofloxacin enhances DNA repair capacity after radiation combined injury
    JULIANN KIANG; Fiscal Year: 2009
  66. Radiation and Genomic Instability in Finite Lifespan Human Mammary Epithelium
    Amy Kronenberg; Fiscal Year: 2010
    ..Work by others demonstrated that a transition to genomic instability occurs at the transition from benign hyperplasia to the earliest stages of malignancy in untreated breast ..
  67. Function & Purification of the Fanconi Anemia Protein C*
    Gary Kupfer; Fiscal Year: 2006
    ..The hallmark of FA is genomic instability, evidenced bv gross chromosomal breakage and DNA alkylating agent hypersensitivity, which correlates with ..
  68. Comparative Mechanisms of Genomic Instability
    Karen M Vasquez; Fiscal Year: 2010
    ..tend to locate in certain genomic fragile site "hotspots", and the effects of environmental agents on the genomic instability at these susceptible hotspots...
  69. Control of Genomic Stability by Emi1 and Securin
    NORMAN LEHMAN; Fiscal Year: 2007
    Aneuploidy and chromosomal aberrations are common features of human neuroplasms. Genomic instability, or the tendency for mitotic errors to create chromosomal duplications, losses, and translocations has long been recognized as a major ..
  70. A novel mouse colon cancer model and chemoprevention
    Wei Dai; Fiscal Year: 2010
    ..An impaired checkpoint function often results in genomic instability, which predisposes cells to malignant transformation...
    Charles Fox; Fiscal Year: 1991
  72. Mechanisms of genomic instability in cancer
    Paul Watt; Fiscal Year: 2002
    ..Since these models employ robust fluorescent screening technology they will be suitable for high throughput industrial application. ..
    Jon Mirsalis; Fiscal Year: 1999 tumors is that tumor progression may be aided by the acquisition of a "mutator" phenotype that produces genomic instability. Gene amplification, microsatellite alterations, and chromosome aberrations have been observed in many ..