chromosome breakage

Summary

Summary: A type of chromosomal aberration which may result from spontaneous or induced breakage. ALKYLATING AGENTS and other chemical MUTAGENS, and various types of RADIATION have been found to cause chromosomal breakage. Breakage can result in translocation; CHROMOSOME INVERSION; or SEQUENCE DELETION.

Top Publications

  1. pmc Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair
    Nicole Bennardo
    Department of Radiation Biology, Beckman Research Institute of City of Hope, Duarte, California, United States of America
    PLoS Genet 4:e1000110. 2008
  2. ncbi ATM and related protein kinases: safeguarding genome integrity
    Yosef Shiloh
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Rev Cancer 3:155-68. 2003
  3. ncbi The pattern of gene amplification is determined by the chromosomal location of hairpin-capped breaks
    Vidhya Narayanan
    School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
    Cell 125:1283-96. 2006
  4. ncbi ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones
    Rita S Cha
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Science 297:602-6. 2002
  5. pmc Unrepaired clustered DNA lesions induce chromosome breakage in human cells
    Aroumougame Asaithamby
    Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 108:8293-8. 2011
  6. pmc An AT-rich sequence in human common fragile site FRA16D causes fork stalling and chromosome breakage in S. cerevisiae
    Haihua Zhang
    Department of Biology, Tufts University, Medford, MA 02155, USA
    Mol Cell 27:367-79. 2007
  7. ncbi Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in tetrahymena
    Kazufumi Mochizuki
    Department of Biology, University of Rochester, Rochester, NY 14627, USA
    Cell 110:689-99. 2002
  8. pmc Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites
    Eliane El Achkar
    Institut Curie, Centre National de la Recherche Scientifique CNRS, Universite Pierre et Marie Curie, Unité Mixte de Recherche 7147, Paris, France
    Proc Natl Acad Sci U S A 102:18069-74. 2005
  9. ncbi BRCA2 is required for homology-directed repair of chromosomal breaks
    M E Moynahan
    Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 7:263-72. 2001
  10. ncbi Mitotic chromosomal instability and cancer: mouse modelling of the human disease
    Juan Manuel Schvartzman
    Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nat Rev Cancer 10:102-15. 2010

Research Grants

  1. Novel therapies for Fanconi anemia
    DAVID A contact WILLIAMS; Fiscal Year: 2010
  2. Roles of the mammalian CST complex in DNA replication and chromosome cohesion
    JASON AARON STEWART; Fiscal Year: 2013
  3. MOLECULAR BASIS OF IMMUNOGLOBULIN HEAVY CHAIN SWITCH
    JANET M STAVNEZER; Fiscal Year: 2013
  4. DGAP: Developmental Genome Anatomy Project
    CYNTHIA CASSON MORTON; Fiscal Year: 2013
  5. DNA REPLICATION AND CHROMOSOME STRUCTURE IN YEAST
    Virginia A Zakian; Fiscal Year: 2013
  6. REPAIR OF GENOME DESTABILIZING DNA STRUCTURES
    Karen M Vasquez; Fiscal Year: 2013
  7. Functions of the BLM Helicase in Telomere Maintenance
    JOANNA LOUISE GRODEN; Fiscal Year: 2012
  8. TRANSPOSASE PROTEIN METNASE IN LEUKEMIC DECATENATION
    Robert A Hromas; Fiscal Year: 2011
  9. Regulation of Caenorhabditis elegans DNA polymerase eta by regulated proteolysis
    Ashley B Williams; Fiscal Year: 2011
  10. Polyploidy, aneuploidy and genome stability
    DAVID S PELLMAN; Fiscal Year: 2013

Detail Information

Publications303 found, 100 shown here

  1. pmc Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair
    Nicole Bennardo
    Department of Radiation Biology, Beckman Research Institute of City of Hope, Duarte, California, United States of America
    PLoS Genet 4:e1000110. 2008
    ..However, at later steps of repair, alt-NHEJ is a mechanistically distinct pathway of DSB repair, and thus may play a unique role in mutagenesis during cancer development and therapy...
  2. ncbi ATM and related protein kinases: safeguarding genome integrity
    Yosef Shiloh
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Rev Cancer 3:155-68. 2003
    ..Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers...
  3. ncbi The pattern of gene amplification is determined by the chromosomal location of hairpin-capped breaks
    Vidhya Narayanan
    School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
    Cell 125:1283-96. 2006
    ..The rules for the palindrome-dependent pathway of gene amplification defined in yeast may operate during the formation of amplicons in human tumors...
  4. ncbi ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones
    Rita S Cha
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Science 297:602-6. 2002
    ..Elimination of Mec1 function leads to genomewide fork stalling followed by chromosome breakage. Breaks do not result from stochastic collapse of stalled forks or other incidental lesions; instead, they ..
  5. pmc Unrepaired clustered DNA lesions induce chromosome breakage in human cells
    Aroumougame Asaithamby
    Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 108:8293-8. 2011
    ..Difficulties associated with clustered DNA damage repair and checkpoint release before the completion of clustered DNA damage repair appear to promote genome instability that may lead to carcinogenesis...
  6. pmc An AT-rich sequence in human common fragile site FRA16D causes fork stalling and chromosome breakage in S. cerevisiae
    Haihua Zhang
    Department of Biology, Tufts University, Medford, MA 02155, USA
    Mol Cell 27:367-79. 2007
    ..Our data suggest that the FRA16D Flex1 sequence causes increased chromosome breakage by forming secondary structures that stall replication fork progression.
  7. ncbi Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in tetrahymena
    Kazufumi Mochizuki
    Department of Biology, University of Rochester, Rochester, NY 14627, USA
    Cell 110:689-99. 2002
    ..We propose that these small RNAs function to specify sequences to be eliminated by a mechanism similar to RNA-mediated gene silencing...
  8. pmc Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites
    Eliane El Achkar
    Institut Curie, Centre National de la Recherche Scientifique CNRS, Universite Pierre et Marie Curie, Unité Mixte de Recherche 7147, Paris, France
    Proc Natl Acad Sci U S A 102:18069-74. 2005
    ....
  9. ncbi BRCA2 is required for homology-directed repair of chromosomal breaks
    M E Moynahan
    Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 7:263-72. 2001
    ..We propose that impaired homology-directed repair caused by BRCA2 deficiency leads to chromosomal instability and, possibly, tumorigenesis, through lack of repair or misrepair of DNA damage...
  10. ncbi Mitotic chromosomal instability and cancer: mouse modelling of the human disease
    Juan Manuel Schvartzman
    Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nat Rev Cancer 10:102-15. 2010
    ..How chromosome instability (CIN) arises in tumours and what consequences it has are still, however, hotly debated issues. Here we review the recent literature with an emphasis on models that recapitulate observations from human disease...
  11. pmc Topoisomerase II- and condensin-dependent breakage of MEC1ATR-sensitive fragile sites occurs independently of spindle tension, anaphase, or cytokinesis
    Nadia Hashash
    Division of Stem Cell Biology and Developmental Genetics, National Institute for Medical Research, Medical Research Council, London, United Kingdom
    PLoS Genet 8:e1002978. 2012
    Fragile sites are loci of recurrent chromosome breakage in the genome. They are found in organisms ranging from bacteria to humans and are implicated in genome instability, evolution, and cancer...
  12. ncbi Evolutionary breakpoints are co-localized with fragile sites and intrachromosomal telomeric sequences in primates
    A Ruiz-Herrera
    Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, Spain
    Cytogenet Genome Res 108:234-47. 2005
    ..More than 80% of these evolutionary breakpoints are located in chromosome bands that express FSs and/or contain ITSs...
  13. ncbi Analysis of a breakpoint cluster reveals insight into the mechanism of intrachromosomal amplification in a lymphoid malignancy
    Paul B Sinclair
    Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle upon Tyne, UK
    Hum Mol Genet 20:2591-602. 2011
    ..These findings provide insight into potential mechanisms involved in the formation of iAMP21...
  14. ncbi A method to produce radiation hybrids for the D-genome chromosomes of wheat (Triticum aestivum L.)
    O Riera-Lizarazu
    Department of Crop and Soil Science, Oregon State University, Corvallis, OR 97331 3002, USA
    Cytogenet Genome Res 129:234-40. 2010
    Radiation hybrid (RH) mapping is based on radiation-induced chromosome breakage rather than meiotic recombination, as a means to induce marker segregation for mapping...
  15. ncbi Transpositions and translocations induced by site-specific double-strand breaks in budding yeast
    James E Haber
    MS029 Rosenstiel Center and Department of Biology, Brandeis University, Waltham, MA 02454 9110, USA
    DNA Repair (Amst) 5:998-1009. 2006
    ..These rearrangements can occur from ectopic gene conversions accompanied by crossing-over, break-induced replication, single-strand annealing or non-homologous end-joining...
  16. ncbi Chromosomal translocation mechanisms at intronic alu elements in mammalian cells
    Beth Elliott
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Mol Cell 17:885-94. 2005
    ..These results emphasize the fluidity of mammalian DSB repair pathway usage. The intron-based system is highly adaptable to addressing a number of issues regarding molecular mechanisms of genomic rearrangements in mammalian cells...
  17. pmc Overcoming natural replication barriers: differential helicase requirements
    Ranjith P Anand
    Department of Biology, Tufts University, Medford, MA 02155, USA
    Nucleic Acids Res 40:1091-105. 2012
    ..Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures...
  18. pmc Aberrant double-strand break repair resulting in half crossovers in mutants defective for Rad51 or the DNA polymerase delta complex
    Catherine E Smith
    Columbia University College of Physicians and Surgeons, Department of Microbiology, New York, NY 10032 2704, USA
    Mol Cell Biol 29:1432-41. 2009
    ..Thus, the BIR defect observed for rad51 mutants is due to strand invasion failure, whereas the Pol delta complex mutants are proficient for strand invasion but unable to complete extensive tracts of recombination-initiated DNA synthesis...
  19. pmc Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication
    Elena V Linardopoulou
    Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North C3 168, Seattle, Washington 98109, USA
    Nature 437:94-100. 2005
    ..More generally, our analyses suggest an evolutionary cycle between segmental polymorphisms and genome rearrangements...
  20. ncbi The limitations of the G1-S checkpoint
    Dorothee Deckbar
    Radiation Biology and DNA Repair, Darmstadt University of Technology, Darmstadt, Germany
    Cancer Res 70:4412-21. 2010
    ....
  21. ncbi SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination
    Alix Kerrest
    Institut Pasteur, Unité de Génétique Moléculaire des Levures, CNRS, URA2171, Universite Pierre et Marie Curie, UFR 927, 25 rue du Dr Roux, F 75015 Paris, France
    Nat Struct Mol Biol 16:159-67. 2009
    ..In the absence of Srs2 or Sgs1, DNA damage accumulates and is processed by homologous recombination, triggering repeat rearrangements...
  22. ncbi New insights to the MLL recombinome of acute leukemias
    C Meyer
    Diagnostic Center of Acute Leukemia, Institute of Pharmaceutical Biology, ZAFES, University of Frankfurt, Frankfurt Main, Germany
    Leukemia 23:1490-9. 2009
    ..Moreover, we describe for the first time the genetic network of reciprocal MLL gene fusions deriving from complex rearrangements...
  23. ncbi DNA breaks promote genomic instability by impeding proper chromosome segregation
    Julia A Kaye
    Cancer Research Institute, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94115, USA
    Curr Biol 14:2096-106. 2004
    ..Here, we have examined the machinery that holds broken chromosome ends together, and we have explored the behavior of broken chromosomes as they pass through mitosis...
  24. pmc High-resolution radiation hybrid map of wheat chromosome 1D
    Venu Kalavacharla
    Department of Bioscience and Biotechnology, Drexel University, Philadelphia, Pennsylvania 19141, USA
    Genetics 173:1089-99. 2006
    ..To date, this is the highest resolution that has been obtained by plant RH mapping and serves as a first step for the development of RH resources in wheat...
  25. ncbi The cellular response to chromosome breakage
    Maria Pia Longhese
    Dipartimento di Biotecnologie e Bioscienze, Universita di Milano Bicocca, 20126 Milan, Italy
    Mol Microbiol 60:1099-108. 2006
    ..Not surprisingly, defects in these networks result in a variety of diseases ranging from severe genetic disorders to cancer predisposition and accelerated ageing...
  26. pmc Genome-wide characterization of tetrahymena thermophila chromosome breakage sites. I. Cloning and identification of functional sites
    Eileen Hamilton
    Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, USA
    Genetics 170:1611-21. 2005
    ..This fragmentation is site specific and directed by a conserved 15-bp chromosome breakage sequence (Cbs element)...
  27. ncbi IgH class switching and translocations use a robust non-classical end-joining pathway
    Catherine T Yan
    Howard Hughes Medical Institute, of Genetics, Boston, Massachusetts 02115, USA
    Nature 449:478-82. 2007
    ..In the absence of C-NHEJ, this alternative end-joining pathway also frequently joins Igh locus breaks to other chromosomes to generate translocations...
  28. pmc RNAi-dependent H3K27 methylation is required for heterochromatin formation and DNA elimination in Tetrahymena
    Yifan Liu
    Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA
    Genes Dev 21:1530-45. 2007
    ..These studies provide a framework for an RNAi-dependent, Polycomb group protein-mediated heterochromatin formation pathway in Tetrahymena and underscore the connection between the two highly conserved machineries in eukaryotes...
  29. pmc Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences
    Jia Lin Ma
    Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245, USA
    Mol Cell Biol 23:8820-8. 2003
    ..The increased gamma ray sensitivity of rad1Delta rad52Delta yku70Delta strains compared to rad52Delta yku70Delta strains suggests that MMEJ also contributes to the repair of DSBs induced by ionizing radiation...
  30. pmc Observation and prediction of recurrent human translocations mediated by NAHR between nonhomologous chromosomes
    Zhishuo Ou
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Genome Res 21:33-46. 2011
    ..Furthermore, we provide a computationally determined genome-wide "recurrent translocation map."..
  31. pmc Palindrome-mediated chromosomal translocations in humans
    Hiroki Kurahashi
    Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470 1192, Japan
    DNA Repair (Amst) 5:1136-45. 2006
    ..We propose that the PATRR adopts a cruciform structure in male meiotic cells, creating genomic instability that leads to the recurrent translocation...
  32. pmc Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress
    Wenyi Feng
    Department of Genome Sciences, University of Washington, Box 355065 Foege Bldg, Room S041, 1705 NE Pacific St, Seattle, Washington 98195, USA
    Genetics 183:1249-60. 2009
    ..Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression...
  33. ncbi ATM stabilizes DNA double-strand-break complexes during V(D)J recombination
    Andrea L Bredemeyer
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nature 442:466-70. 2006
    ....
  34. ncbi High-resolution mapping of crossovers in human sperm defines a minisatellite-associated recombination hotspot
    A J Jeffreys
    Department of Genetics, University of Leicester, United Kingdom
    Mol Cell 2:267-73. 1998
    ....
  35. doi Gene amplification mechanisms
    Michelle Debatisse
    UMR 7147, Institut Curie, CNRS, Universite Pierre et Marie Curie, Paris, France
    Adv Exp Med Biol 570:343-61. 2005
  36. pmc Dicentric breakage at telomere fusions
    Sabrina Pobiega
    Commissariat a l Energie Atomique, Direction des Sciences du Vivant, Institut de Radiobiologie Cellulaire et Moleculaire, Service Instabilité Génétique Réparation et Recombinaison, Laboratoire Télmère et Réparation du Chromosome, Fontenay aux roses 92260, France
    Genes Dev 24:720-33. 2010
    ..This unforeseen result suggests a rescue pathway able to process telomere fusions and to back up NHEJ inhibition at telomeres...
  37. pmc Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificity
    Albert G Tsai
    Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, MC9176, Los Angeles, CA 90089 9176, USA
    Cell 135:1130-42. 2008
    ....
  38. ncbi Are aneuploidy and chromosome breakage caused by a CINgle mechanism?
    Carlos Martinez-A
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia CSIC, Madrid, Spain
    Cell Cycle 9:2275-80. 2010
    ..Since a poorly controlled spindle can cause merotelic attachments, kinetochore distortion, and subsequent chromosome breakage, spindle defects can generate the sticky ends necessary to start a breakage-fusion-bridge cycle...
  39. ncbi Chromosome fragility: molecular mechanisms and cellular consequences
    Catherine H Freudenreich
    Department of Biology and Program in Genetics, Tufts University, Medford, MA 02155, USA
    Front Biosci 12:4911-24. 2007
    ..An understanding of these events will provide insight into the generation of cancer, since deletions and rearrangements at human common fragile sites and associated tumor suppressor genes are an early event in tumorigenesis...
  40. pmc Limiting the persistence of a chromosome break diminishes its mutagenic potential
    Nicole Bennardo
    Department of Cancer Biology, Division of Radiation Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA
    PLoS Genet 5:e1000683. 2009
    ..Furthermore, we find that individual genetic factors play distinct roles during repair of non-cohesive DSB ends that are generated via co-expression of I-SceI with Trex2...
  41. ncbi Homology-directed dna repair, mitomycin-c resistance, and chromosome stability is restored with correction of a Brca1 mutation
    M E Moynahan
    Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
    Cancer Res 61:4842-50. 2001
    ..We conclude that the inability to properly repair strand breaks by homology-directed repair gives rise to defects in chromosome maintenance that promote genetic instability and, it is likely, tumorigenesis...
  42. ncbi Initiation of the breakage-fusion-bridge mechanism through common fragile site activation in human breast cancer cells: the model of PIP gene duplication from a break at FRA7I
    Marina Ciullo
    Génomique Fonctionnelle et Biologie Systémique en Santé, FRE 2571, Centre National de la Recherche Scientifique, 19 rue Guy Moquet, 94801 Villejuif, France
    Hum Mol Genet 11:2887-94. 2002
    ..T47D cells thus offer a unique opportunity to observe the earliest products of the BFB cycle mechanism. Our findings constitute the first evidence that this amplification mechanism can be initiated in vivo by fragile site activation...
  43. ncbi Ejaculated and epididymal mouse spermatozoa are different in their susceptibility to nuclease-dependent DNA damage and in their nuclease activity
    Yasuhiro Yamauchi
    Institute for Biogenesis Research, University of Hawaii Medical School, Honolulu, Hawaii 96822, USA
    Biol Reprod 77:636-47. 2007
    ..This nuclease activity was detected both in the sperm-free fraction of preparations and isolated sperm...
  44. ncbi Pericentromeric instability and spontaneous emergence of human neoacrocentric and minute chromosomes in the alternative pathway of telomere lengthening
    Sarantis Gagos
    Laboratory of Genetics, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
    Cancer Res 68:8146-55. 2008
    ..These observations are important in understanding the global genomic instability that characterizes most human advanced malignancies...
  45. ncbi Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome
    Andrew J Sharp
    Department of Genome Sciences and the Howard Hughes Medical Institute, University of Washington School of Medicine, 1705 NE Pacific St, Seattle, Washington 98195, USA
    Nat Genet 38:1038-42. 2006
    ..In common with the 17q21.31 deletion, these breakpoint regions are sites of copy number polymorphism in controls, indicating that these may be inherently unstable genomic regions...
  46. ncbi A highly complex chromosomal rearrangement between five chromosomes in a healthy female diagnosed in preparation for intracytoplasmatic sperm injection
    Alma Kuechler
    Institute of Human Genetics and Anthropology, Kollegiengasse 10, D 07743 Jena, Germany
    J Histochem Cytochem 53:355-7. 2005
    ....
  47. ncbi Chromosome breakage in human preimplantation embryos from carriers of structural chromosomal abnormalities in relation to fragile sites, maternal age, and poor sperm factors
    L Xanthopoulou
    UCL Centre for PGD, Institute for Women s Health, University College London, London, UK
    Cytogenet Genome Res 136:21-9. 2012
    b>Chromosome breakage is a fairly widespread phenomenon in preimplantation embryos affecting at least 10% of day 3 cleavage stage embryos. It may be detected during preimplantation genetic diagnosis (PGD)...
  48. ncbi Telomeres and radiation-induced chromosome breakage
    P Slijepcevic
    School of Biological and Medical Sciences, University of St Andrews, UK
    Mutagenesis 13:45-9. 1998
    ....
  49. pmc Inhibition of topoisomerase I prevents chromosome breakage at common fragile sites
    Martin F Arlt
    Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
    DNA Repair (Amst) 9:678-89. 2010
    ..These data from cultured human cells demonstrate that topoisomerase I activity is required for DNA common fragile site breaks and suggest that polymerase-helicase uncoupling is a key initial event in this process...
  50. pmc Breakpoint regions and homologous synteny blocks in chromosomes have different evolutionary histories
    Denis M Larkin
    Department of Animal Sciences, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Genome Res 19:770-7. 2009
    ..These results demonstrate that chromosome breakage in evolution is nonrandom and that HSBs and EBRs are evolving in distinctly different ways...
  51. ncbi A translocation breakpoint cluster disrupts the newly defined 3' end of the SNURF-SNRPN transcription unit on chromosome 15
    J Wirth
    Max Planck Institut fur Molekulare Genetik
    Hum Mol Genet 10:201-10. 2001
    ..Our data suggest that lack of expression of these sequences contributes to the PWS phenotype...
  52. pmc FRA18C: a new aphidicolin-inducible fragile site on chromosome 18q22, possibly associated with in vivo chromosome breakage
    Kim Debacker
    J Med Genet 44:347-52. 2007
    ..The breakpoint region was highly enriched in AT-rich sequences. It is the first report of an aphidicolin-sensitive fragile site that coincides with an in vivo chromosome truncation in the progeny...
  53. pmc Irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture
    Aroumougame Asaithamby
    Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas, Southwestern Medical Centre, Dallas, TX 75390, USA
    Nucleic Acids Res 39:5474-88. 2011
    ..Our data suggest that downregulation of multiple DNA repair pathway genes in differentiated cells renders them vulnerable to DSBs, promoting genome instability that may lead to carcinogenesis...
  54. ncbi Differential usage of non-homologous end-joining and homologous recombination in double strand break repair
    Eiichiro Sonoda
    Radiation Genetics, Graduate School of Medicine, Kyoto University, Konoe Yoshida, Kyoto 606 8501, Japan
    DNA Repair (Amst) 5:1021-9. 2006
    ..This active NHEJ requires a regulatory mechanism to choose HR or NHEJ in vertebrate cells. In this review, we illustrate how HR and NHEJ are differentially regulated depending on the phase of cell cycle and on the nature of the DSB...
  55. pmc Molecular and fluorescence in situ hybridization characterization of the breakpoints in 46 large supernumerary marker 15 chromosomes reveals an unexpected level of complexity
    S E Roberts
    Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, United Kingdom
    Am J Hum Genet 73:1061-72. 2003
    ..This suggests that multiple mechanisms are involved in the formation of large SMC(15)s...
  56. ncbi Role of haemoglobin in the protection of cultured lymphocytes against diepoxybutane (DEB), assessed by in vitro induced chromosome breakage
    Beatriz Porto
    Laboratory of Cytogenetics, Instituto Ciências Biomédicas Abel Salazar ICBAS, Largo do Prof Abel Salazar, No 2, 4099 003, Porto, Portugal
    Mutat Res 536:61-7. 2003
    ..influence of individual GSTM1 and GSTT1 genotypes and the presence of RBC on the frequency of DEB-induced chromosome breakage in lymphocyte cultures from normal individuals and, in particular, the influence of isolated components of ..
  57. ncbi Template switching during break-induced replication
    Catherine E Smith
    Department of Microbiology, Columbia University Medical Center, 701 West 168th Street, New York, New York 10032, USA
    Nature 447:102-5. 2007
    ..This dynamic process could function to promote gene conversion by capture of the displaced invading strand at two-ended DSBs to prevent BIR...
  58. ncbi Chromosome breakage syndromes and cancer
    Nahum J Duker
    Laboratory Medicine, Fels Institute for Cancer Research and Molecular Biology, Philadelphia, PA 19140, USA
    Am J Med Genet 115:125-9. 2002
    ..Each defect involves a separate protein in these complex pathways...
  59. ncbi Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex
    Kirill Lobachev
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, 101 Alexander Drive, Research Triangle Park, NC 27709 USA
    Curr Biol 14:2107-12. 2004
    ..Thus, the RMX complex holds broken ends together and counteracts mitotic spindle forces that can be destructive to damaged chromosomes...
  60. pmc Epigenetic control of chromosome breakage at the 5' end of Paramecium tetraurelia gene A
    Laurence Amar
    UMR 8080, IBAIC, Bat 444, 91405 Orsay Cedex, France
    Eukaryot Cell 3:1136-46. 2004
    ..We propose that the d48 factor(s) may be derived from RNA molecules transcribed from the Ad48 Mac ends and encompassing the truncated A gene and telomeric repeats...
  61. pmc Chromosome breakage is regulated by the interaction of the BLM helicase and topoisomerase IIalpha
    Beatriz Russell
    Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine, Columbus, Ohio 45229, USA
    Cancer Res 71:561-71. 2011
    ..Deletion of the interaction domain from BLM fails to correct the elevated chromosome breakage of transfected BLM-deficient cells...
  62. ncbi Translocation and gross deletion breakpoints in human inherited disease and cancer I: Nucleotide composition and recombination-associated motifs
    Shaun S Abeysinghe
    Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK
    Hum Mutat 22:229-44. 2003
    ..Our results are therefore consistent with a role for homologous unequal recombination in deletion mutagenesis and a role for nonhomologous recombination in the generation of translocations...
  63. ncbi Tp53 codon-72 polymorphisms identify different radiation sensitivities to g2-chromosome breakage in human lymphoblast cells
    Jeffrey L Schwartz
    Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington, USA
    Environ Mol Mutagen 52:77-80. 2011
    ..Distinguishing the effect of TP53 codon-72 variations from other modifiers of G2-chromosome radiosensitivity might aid in identifying new markers of cancer risk...
  64. ncbi Genetic alterations in cancer as a result of breakage at fragile sites
    Nicholas C Popescu
    Molecular Cytogenetics Section, Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20814 4958, USA
    Cancer Lett 192:1-17. 2003
    ....
  65. pmc Chromosome breakage after G2 checkpoint release
    Dorothee Deckbar
    Fachrichtung Biophysik, Universitat des Saarlandes, 66421 Homburg Saar, Germany
    J Cell Biol 176:749-55. 2007
    ..This represents a major contribution to chromosome breakage. The presence of chromosome breaks in cells released from checkpoint arrest suggests that release occurs ..
  66. ncbi When, where and how the bridge breaks: anaphase bridge breakage plays a crucial role in gene amplification and HSR generation
    Noriaki Shimizu
    Faculty of Integrated Arts and Sciences, Hiroshima University, Hiroshima 739 8521, Japan
    Exp Cell Res 302:233-43. 2005
    ..The unbroken bridge appeared to inhibit the completion of cytokinesis. These observations strongly suggest that anaphase bridges are highly elastic and that the length of the spindle axis determines the maximal HSR length...
  67. pmc Principles of genome evolution in the Drosophila melanogaster species group
    Jose M Ranz
    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    PLoS Biol 5:e152. 2007
    ..Outgroup analysis also revealed evidence for widespread breakpoint recycling. Lastly, we have found that expression domains in D. melanogaster may be disrupted in D. yakuba, bringing into question their potential adaptive significance...
  68. ncbi The breakage-fusion-bridge (BFB) cycle as a mechanism for generating genetic heterogeneity in osteosarcoma
    Shamini Selvarajah
    Department of Pathology and Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada
    Chromosoma 115:459-67. 2006
    ....
  69. ncbi Human chromosome 15q11-q14 regions of rearrangements contain clusters of LCR15 duplicons
    Miguel Angel Pujana
    Centre de Genètica Mèdica i Molecular IRO, Hospital Duran i Reynals, Gran Via Km 2 7, 08907 L Hospitalet de Llobregat, Barcelona, Spain
    Eur J Hum Genet 10:26-35. 2002
    ..LCR15 analysis in non-human primates and age-sequence divergences support a recent origin of this family of segmental duplications through human speciation...
  70. pmc A model of oncogenic rearrangements: differences between chromosomal translocation mechanisms and simple double-strand break repair
    David M Weinstock
    Department of Medicine and Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Blood 107:777-80. 2006
    ..Interestingly, in a direct comparison, the spectrum of translocation breakpoint junctions differed from junctions derived from repair at a single chromosomal break, providing mechanistic insight into translocation formation...
  71. pmc Chromosome breakage in the Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints
    J M Amos-Landgraf
    Department of Genetics, Case Western Reserve University School of Medicine, and Center for Human Genetics, University Hospitals of Cleveland, Cleveland, OH 44106 4955, USA
    Am J Hum Genet 65:370-86. 1999
    ..Furthermore, we propose that active transcription of these repeats in male and female germ cells may facilitate the homologous recombination process...
  72. ncbi Characterization of chromosomal inversion of the mouse hairy ears (Eh) mutation associated with cleft palate
    Kentaro Katayama
    Graduate School of Natural Science and Technology, Okayama University, Tsushima Naka, Okayama 700 8530, Japan
    Mamm Genome 18:246-54. 2007
    ....
  73. ncbi Apoptotic stimuli initiate MLL-AF9 translocations that are transcribed in cells capable of division
    Christopher J Betti
    Program in Molecular Biology, Maywood, Illinois 60153, USA
    Cancer Res 63:1377-81. 2003
    ..These data are consistent with a novel pathogenic role for the apoptotic program where translocations with leukemogenic potential are created within cells that have the capacity to divide...
  74. ncbi gammaH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes
    Manuel Stucki
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
    DNA Repair (Amst) 5:534-43. 2006
    ....
  75. ncbi Molecular analysis of a constitutional complex genome rearrangement with 11 breakpoints involving chromosomes 3, 11, 12, and 21 and a approximately 0.5-Mb submicroscopic deletion in a patient with mild mental retardation
    Katarzyna Borg
    Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01 211, Warsaw, Poland
    Hum Genet 118:267-75. 2005
    ..Other potential genes responsible for intellectual deficiency disrupted as a result of patient's chromosomal rearrangement map at 12q14.1 (TAFA2), 12q23.1 (METAP2), and 11p14.1 (BDNF)...
  76. ncbi Increased rates of chromosome breakage in BRCA1 carriers are normalized by oral selenium supplementation
    Elzbieta Kowalska
    Centre for Research in Women s Health, 790 Bay Street, Toronto, Ontario, Canada, M5G 1N8
    Cancer Epidemiol Biomarkers Prev 14:1302-6. 2005
    ..40 versus 0.39). Oral selenium is a good candidate for chemoprevention in women who carry a mutation in the BRCA1 gene...
  77. pmc Alternative pathways for the repair of RAG-induced DNA breaks
    David M Weinstock
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Mol Cell Biol 26:131-9. 2006
    ..Thus, RAG-generated DSBs are typically repaired by the NHEJ pathway in ES cells, but in the absence of NHEJ components, a substantial fraction of breaks can be efficiently channeled into alternative pathways in these cells...
  78. ncbi Alternative translocation breakpoint cluster region 5' to BCL-6 in B-cell non-Hodgkin's lymphoma
    Marion P Butler
    Institute for Cancer Genetics, and the Department of Pathology, Columbia University, New York, NY 10032, USA
    Cancer Res 62:4089-94. 2002
    ..The identification of BCL-6 ABR provides new tools for the diagnosis of lymphomas carrying aberrations at 3q27 and deregulated BCL-6 genes...
  79. pmc The fragile breakage versus random breakage models of chromosome evolution
    Qian Peng
    Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA
    PLoS Comput Biol 2:e14. 2006
    ..Finally, we study the link between rearrangements and regulatory regions and argue that long regulatory regions and inhomogeneity of gene distribution in mammalian genomes may be responsible for the breakpoint reuse phenomenon...
  80. ncbi Saccharomyces cerevisiae ATM orthologue suppresses break-induced chromosome translocations
    Kihoon Lee
    Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245, USA
    Nature 454:543-6. 2008
    ....
  81. pmc Cryptic deletions are a common finding in "balanced" reciprocal and complex chromosome rearrangements: a study of 59 patients
    M de Gregori
    Biologia Generale e Genetica Medica, Universitè di Pavia, Pavia, Italy
    J Med Genet 44:750-62. 2007
    ....
  82. ncbi Increased radiation-induced chromosome breakage after progesterone addition at the G1/S-phase transition
    M Ricoul
    CEA, Laboratoire de Radiobiologie et Oncologie, DRR, DSV, Fontenay aux Roses, France
    Mutat Res 403:177-83. 1998
    ..Cultures with an increased frequency of chromosome breakage had a slightly higher mitotic index than controls...
  83. ncbi Evaluation of chromosome breakage and DNA integrity in sperm: an investigation of remote semen collection conditions
    Karen E Young
    Molecular Toxicology Program, Center for Occupational and Environmental Health, School of Nursing, University of California, Los Angeles, USA
    J Androl 24:853-61. 2003
    ..The mean frequency of chromosome breakage per 10 000 cells scored in sperm-FISH for FF and F24 was 10.5 +/- 1.3 breaks and 11.2 +/- 1...
  84. ncbi A non-B-DNA structure at the Bcl-2 major breakpoint region is cleaved by the RAG complex
    Sathees C Raghavan
    Norris Comprehensive Cancer Center, Room 5428, University of Southern California Keck School of Medicine, 1441 Eastlake Ave, MC9176, Los Angeles, California 90033, USA
    Nature 428:88-93. 2004
    ..Hence, a stable non-B-DNA structure in the human genome appears to be the basis for the fragility of the Bcl-2 Mbr, and the RAG complex is able to cleave this structure...
  85. ncbi Jumping translocations are common in solid tumor cell lines and result in recurrent fusions of whole chromosome arms
    H M Padilla-Nash
    Genetics Department, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genes Chromosomes Cancer 30:349-63. 2001
    ..consequently resulting in tumor-specific genomic imbalances. Published 2001 Wiley-Liss, Inc...
  86. pmc Genomic disorders on 22q11
    Heather E McDermid
    Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
    Am J Hum Genet 70:1077-88. 2002
    ..Research on genomic disorders on 22q11 will continue to expand our knowledge of the mechanisms of chromosomal rearrangements and the molecular basis of their phenotypic consequences...
  87. ncbi Molecular processes of chromosome 9p21 deletions causing inactivation of the p16 tumor suppressor gene in human cancer: deduction from structural analysis of breakpoints for deletions
    Takashi Kohno
    Biology Division, National Cancer Center Research Institute, Tokyo, Japan
    DNA Repair (Amst) 5:1273-81. 2006
    ..Further structural analysis of other hot spots of chromosomal DNA breaks as well as the evaluation of the activity and specificity of NHEJ in human cells will elucidate the mechanisms of chromosome interstitial deletions in human cells...
  88. pmc Testing chromosomal phylogenies and inversion breakpoint reuse in Drosophila
    Josefa González
    Departament de Genetica i de Microbiologia, Universitat Autonoma de Barcelona, 08193 Bellaterra Barcelona, Spain
    Genetics 175:167-77. 2007
    ..We also estimated the rate of rearrangement between D. repleta and D. buzzatii and conclude that rates within the genus Drosophila vary substantially between lineages, even within a single species group...
  89. pmc Recurring genomic breaks in independent lineages support genomic fragility
    Hanno Hinsch
    Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA, USA
    BMC Evol Biol 6:90. 2006
    ..In contrast, we investigate whether this regional fragility is an inherent genomic characteristic and is thus conserved over multiple independent lineages...
  90. ncbi Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations: delineation of 7q21.11 breakpoints
    Stefan Vermeulen
    Center for Medical Genetics, Ghent University Hospital 0K5, De Pintelaan 185, 9000 Ghent, Belgium
    Am J Med Genet A 124:10-8. 2004
    ..The other patient had a breakpoint more proximal to this region. The present data together with these from the literature provide evidence that a region within 7q21.11 may be prone to breakage and formation of CCRs...
  91. pmc Independent intrachromosomal recombination events underlie the pericentric inversions of chimpanzee and gorilla chromosomes homologous to human chromosome 16
    Violaine Goidts
    Department of Human Genetics, University of Ulm, 89081 Ulm, Germany
    Genome Res 15:1232-42. 2005
    ..Thus, the most parsimonious interpretation is that the gorilla and chimpanzee homologs exhibit similar but nonidentical derived pericentric inversions, whereas HSA 16 represents the ancestral form among hominoids...
  92. ncbi The Drosophila Mre11/Rad50 complex is required to prevent both telomeric fusion and chromosome breakage
    Laura Ciapponi
    Dipartimento di Genetica e Biologia Molecolare and Istituto di Biologia e Patologia Molecolari del Consiglio Nazionale delle Ricerche, Universita di Roma La Sapienza, 00185 Rome, Italy
    Curr Biol 14:1360-6. 2004
    ..Here, we show that null mutations in the Drosophila mre11 and rad50 genes cause both telomeric fusion and chromosome breakage. Moreover, we demonstrate that these mutations are in the same epistasis group required for telomere ..
  93. pmc Reconstructing the genomic architecture of ancestral mammals: lessons from human, mouse, and rat genomes
    Guillaume Bourque
    Centre de Recherches Mathématiques, Universite de Montreal, Canada H3C 3J7
    Genome Res 14:507-16. 2004
    ..Our analysis implies that the rate of rearrangements is much higher in murid rodents than in the human lineage and confirms the existence of rearrangement hot-spots in all three lineages...
  94. ncbi Chromosomal breakpoint reuse in genome sequence rearrangement
    David Sankoff
    Department of Mathematics and Statistics, University of Ottawa, 585 King Edward Avenue, Ottawa, Ontario, Canada K1N 6N5
    J Comput Biol 12:812-21. 2005
    ..Analytic and simulation methods show that reuse is very sensitive to the proportion of blocks excluded. As is pertinent to the comparison of mammalian genomes, this exclusion risks randomizing the comparison partially or entirely...
  95. pmc Hotspots of mutation and breakage in dog and human chromosomes
    Caleb Webber
    MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom
    Genome Res 15:1787-97. 2005
    ..Rather, we propose that high G+C sequences are found preferentially within dog subtelomeres as a direct consequence of chromosomal fission occurring more frequently within regions elevated in G+C...
  96. pmc Breakpoints of gross deletions coincide with non-B DNA conformations
    Albino Bacolla
    Institute of Biosciences and Technology, Center for Genome Research, Texas A and M University System Health Science Center, Texas Medical Center, 2121 Holcombe Boulevard, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 101:14162-7. 2004
    ..In 11 deletions analyzed, breakpoints were explicable by non-B DNA structure formation. We conclude that alternative DNA conformations trigger genomic rearrangements through recombination-repair activities...
  97. pmc Hotspots of mammalian chromosomal evolution
    Jeffrey A Bailey
    Department of Genetics, Center for Computational Genomics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106, USA
    Genome Biol 5:R23. 2004
    ..With the availability of both the human and mouse genomic sequences, detailed analysis of the sequence properties underlying these breakpoints is now possible...
  98. ncbi H2AX prevents DNA breaks from progressing to chromosome breaks and translocations
    Sonia Franco
    Howard Hughes Medical Institute, The Children s Hospital, Department of Genetics, Harvard Medical School and the CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA
    Mol Cell 21:201-14. 2006
    ..As cellular p53 status does not markedly influence the frequency of such events, our results also have implications for how p53 and the DSB response machinery cooperate to suppress generation of lymphomas with oncogenic translocations...
  99. ncbi Should chromosome breakage studies be performed in patients with VACTERL association?
    Laurence Faivre
    Centre de Genetique, Hôpital d Enfants, Dijon, France
    Am J Med Genet A 137:55-8. 2005
    ..Although VACTERL with hydrocephaly has clearly been associated with FA, the indication for chromosome breakage studies is not clear in VACTERL without hydrocephaly...
  100. pmc Breakpoint structure reveals the unique origin of an interspecific chromosomal inversion (2La) in the Anopheles gambiae complex
    Igor V Sharakhov
    Center for Tropical Disease Research and Training, Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA
    Proc Natl Acad Sci U S A 103:6258-62. 2006
    ..The derived position of 2L+a, long considered ancestral in this medically important group, has significant implications for the phylogenetic history and the evolution of vectorial capacity in the A. gambiae complex...
  101. ncbi Breakpoint analysis of the pericentric inversion between chimpanzee chromosome 10 and the homologous chromosome 12 in humans
    H Kehrer-Sawatzki
    Department of Human Genetics, University of Ulm, Germany
    Cytogenet Genome Res 108:91-7. 2005
    ..These findings coincide with the trend observed in hominoid karyotype evolution that humans have a karyotype close to an ancestral one, while African great apes present with more derived chromosome arrangements...

Research Grants64

  1. Novel therapies for Fanconi anemia
    DAVID A contact WILLIAMS; Fiscal Year: 2010
    ....
  2. Roles of the mammalian CST complex in DNA replication and chromosome cohesion
    JASON AARON STEWART; Fiscal Year: 2013
    ..Several genetic disorders, termed cohesionopathies, are also associated with SCC loss and chromosome breakage. Furthermore, mutations in CTC1 were recently shown to underlie a rare autosomal recessive disorder, Coats ..
  3. MOLECULAR BASIS OF IMMUNOGLOBULIN HEAVY CHAIN SWITCH
    JANET M STAVNEZER; Fiscal Year: 2013
    ..We will investigate what makes these other sites targets for AID, and for DNA break formation. Thus our studies will also shed light on the important question of how AID chooses its targets. ..
  4. DGAP: Developmental Genome Anatomy Project
    CYNTHIA CASSON MORTON; Fiscal Year: 2013
    ....
  5. DNA REPLICATION AND CHROMOSOME STRUCTURE IN YEAST
    Virginia A Zakian; Fiscal Year: 2013
    ..we will again use genome wide approaches, which will identify Pfh1 binding sites, as well as sites of chromosome breakage upon Pfh1 depletion...
  6. REPAIR OF GENOME DESTABILIZING DNA STRUCTURES
    Karen M Vasquez; Fiscal Year: 2013
    ....
  7. Functions of the BLM Helicase in Telomere Maintenance
    JOANNA LOUISE GRODEN; Fiscal Year: 2012
    ..Cells from BS individuals are characterized by chromosome breakage and other chromosomal anomalies that are indicative of increased somatic recombination...
  8. TRANSPOSASE PROTEIN METNASE IN LEUKEMIC DECATENATION
    Robert A Hromas; Fiscal Year: 2011
    ..Preventing such chromosome breakage can reduce the mutations that cause many forms of cancer...
  9. Regulation of Caenorhabditis elegans DNA polymerase eta by regulated proteolysis
    Ashley B Williams; Fiscal Year: 2011
    ..stalled replication forks can have serious effects on cells, including interruptions in the cell cycle and chromosome breakage. Thus, UV-induced DNA lesions can destabilize the genome, increasing the chance of mutations...
  10. Polyploidy, aneuploidy and genome stability
    DAVID S PELLMAN; Fiscal Year: 2013
    ....
  11. Suppression of translocations by RecQ-like DNA helicases
    KRISTINA HILDEGARD SCHMIDT; Fiscal Year: 2012
    ..of genome integrity and will shed light on the general mechanisms leading to chromosomal rearrangements, especially gene translocations, which are often associated with human cancers and chromosome breakage syndromes.
  12. Regulation of the DNA damage response by ATM-MRN pathway
    Jean Gautier; Fiscal Year: 2013
    ..of interaction with reactive oxygen species, collapse of stalled replication forks, telomere dysfunction, chromosome breakage during anaphase, or following programmed genomic rearrangements during immune and germ cell maturation...
  13. GENOTOXICITY OF CHROMIUM COMPOUNDS
    Anatoly Zhitkovich; Fiscal Year: 2013
    ..abstract_text> ..
  14. Validation and extension of an existing risk model for lung cancer
    Carol J Etzel; Fiscal Year: 2010
    ..Evaluation of these chromosomal endpoints in an independent sample will provide proof-of-principle for subsequent inclusion of additional functional phenotypes and genotypes into the model. ..
  15. Mechanism of PCNA Polyubiquitination
    CHRISTOPHER EDWARD BERNDSEN; Fiscal Year: 2010
    ..The functions of HLTF and SHPRH are likely linked to their role in polyubiquitination of PCNA and the initiation of error-free DNA damage tolerance. ..
  16. Epigenetic Regulation of Drosophila Telomere Function
    Michael H Brodsky; Fiscal Year: 2012
    ..Given that both HP1 and DNA damage response pathways play roles at human telomeres, understanding telomere function in Drosophila may lead to new ways to shorten or extend telomeres in humans. ..
  17. Chromatin Diminution in Ascaris
    Richard E Davis; Fiscal Year: 2013
    ..The elimination results in chromosome breakage and the loss of chromosome termini as well as the generation of new chromosomes...
  18. Single Stranded DNA: The Genome's Achilles Heel
    Wenyi Feng; Fiscal Year: 2009
    ..In the long term, I hope that this research will aid in promoting the development of diagnostic and treatment tools for human diseases. ..
  19. Mechanism of subtelomeric breaks
    MARY KATHARINE RUDD; Fiscal Year: 2013
    ..Despite the impact on human health, very little is known about the mechanisms of chromosome breakage and repair that give rise to subtelomeric CNV...
  20. Base Analog Toxicity and Detoxification
    Andrei Kuzminov; Fiscal Year: 2012
    ..The proposed research will lead to a better understanding of the clastogenic potential of base analogs, as well as to elucidation of the chromosomal breakage-avoidance strategies of the cell. ..
  21. Role of regulation of eukaryotic DNA replication in preserving genomic stability
    Joachim J Li; Fiscal Year: 2013
    ..These data will significantly enhance our understanding of how re-replication promotes genomic instability, as well as give insight into the biological significance of loss of replication control. ..
  22. Single Stranded DNA: The Genome's Achilles Heel
    Wenyi Feng; Fiscal Year: 2013
    ..Investigate the link between extensive ssDNA formation during replication stress and chromosome breakage using the genome-wide ssDNA and chromosome breakage mapping techniques developed by the applicant in ..
  23. Resolution of Complex Breaks by Nonhomologous End Joining
    Dale A Ramsden; Fiscal Year: 2013
    ..In Aim 3 we will determine how NHEJ regulates the fidelity of the ligation step, and what impact regulation of fidelity has on resolution of complex end structures. ..
  24. Sperm DNA damage in fertilization
    MONIKA WARD; Fiscal Year: 2006
    ..breaks, examine early post-fertilization events after ICSI with treated spermatozoa, and test if paternal chromosome breakage can be observed in the absence of ICSI, to exclude the possibility that observed chromosome breakage is an ..
  25. Novel Molecular and Cellular Therapies in Fanconi Anemia
    David Williams; Fiscal Year: 2009
    ..This grant proposal seeks funding to conduct these clinical trials and further develop retrovirus-mediated complementation analysis in a CAP/CLIA environment for use in clinical management of FA patients. ..
  26. RADIATION CYTOGENETICS
    Joel Bedford; Fiscal Year: 1993
    ..studies of the nature of lesions that lead to aberration formation including an investigation of interphase chromosome breakage as expressed in prematurely condensed chromosomes (PCCs) as well as mitotic chromosomes...
  27. PHENYTOIN PATHOGENESIS OF GINGIVAL OVERGROWTH
    Thomas Hassell; Fiscal Year: 1990
    ..The cat breeding study will continue to enhance the human twin experiments. Cytogenetic analyses (e.g., chromosome breakage, sister chromatid exchange) will be performed on fibroblasts from overgrown gingiva, with and without in ..
  28. REPLICATION AND AMPLIFICATION OF TETRAHYMENA RDNA
    Geoffrey Kapler; Fiscal Year: 2000
    ..rDNA amplification occurs as part of a developmental program, accompanied by chromosome breakage and DNA rearrangement, similar to mammalian amplification events...
  29. MOLECULAR GENETIC ANALYSIS OF XQ28
    Stephen Warren; Fiscal Year: 1992
    ..this will be accomplished by inducing, in the hybrid cells, chromosome breakage at the fragile X site (Xq27...
  30. DNA Polymerases in Nonhomologous End Joining
    Dale A Ramsden; Fiscal Year: 2013
    ..Our results will provide a better framework for predicting the mutagenic side effects of cancer therapy, and help inform the appropriate application of therapy adjuncts that target specific repair pathways. ..
  31. MOLECULAR MECHANISMS IN SCLERODERMA--SCL-70/TOPO I
    Angeline Douvas; Fiscal Year: 1990
    ..Based on the outcome of these studies it may be possible to design more specific and effective therapies for this disorder...
  32. REGULATION OF MITOSIS IN NORMAL AND TRANSFORMED CELLS
    Robert Schlegel; Fiscal Year: 1993
    ....
  33. Gamma-ray-induced mutagen sensitivity in breast cancer
    Li E Wang; Fiscal Year: 2005
    ....
  34. MECHANISMS AND CONSEQUENCES OF CHROMOSOMAL ABNORMALITIES
    David Ledbetter; Fiscal Year: 2002
    ..Evidence now suggests the presence of four hotspots for chromosome breakage in this region: two proximal to the PWS/AS region and two distal...
  35. PROBING THE DNA DAMAGE RESPONSE IN VITRO
    Jean Gautier; Fiscal Year: 2006
    ..Failure to activate or to coordinate the DNA-damage induced signal transduction pathways can lead to chromosome breakage and loss, and to the propagation of mutations...
  36. AMPLIFICATION--MODEL FOR GENETIC INSTABILITY IN CANCER
    JOYCE HAMLIN; Fiscal Year: 2005
    ..abstract_text> ..
  37. ULTRAVIOLET AND IONIZING RADIATION DAMAGE
    HENRY GRIGGS; Fiscal Year: 1990
    ..This approach is yielding dose-survival, dose-chromosome breakage, and dose-aberrational kinetics which appear essential for a more complete description of relations between ..
  38. Systematic Profiling of Nonhomologous End Joining in Cancer
    Dale A Ramsden; Fiscal Year: 2013
    ..We will determine the extent of cancer-associated variation in NHEJ, and whether this variation could help predict therapy outcome and aid in development of better (rationally designed and targeted) therapies. ..
  39. MECHANISMS OF DNA DAMAGE TRIGGERED S PHASE CHECKPOINTS
    Thomas Melendy; Fiscal Year: 2005
    ....
  40. Analysis of regulation and function of the BLM helicase
    Nathan Ellis; Fiscal Year: 2003
    ..Absence of the BLM helicase from a cell causes a striking genomic instability that includes both chromosome breakage and excessive chromatid exchange, in particular, sister chromatid exchange (SCE)...
  41. Function & Purification of the Fanconi Anemia Protein C*
    Gary Kupfer; Fiscal Year: 2006
    ..Identification of new proteins and elucidation of FA pathway mechanisms promise to shed light on a novel area of cancer biology with the potential to provide direct clinical applicability. ..
  42. Characterization of the DNA replication protein Sid2p
    Elizabeth Vallen; Fiscal Year: 2002
    ..Although Sic1p is not essential, strains deleted for sic1 demonstrate an increased frequency of chromosome breakage and loss...
  43. IMMUNOLOGICAL CHARACTERIZATION OF CELLS
    Emmanuel Akporiaye; Fiscal Year: 1992
    ..The general hypothesis to be tested is that chromosome breakage and rearrangement facilitate induction of resistance to chemotherapeutic agents...
  44. X-IRRADIATION, DRUG RESISTANCE AND GENE AMPLIFICATION
    Peter Hahn; Fiscal Year: 1992
    ..The general hypothesis to be tested is that chromosome breakage and rearrangement facilitate induction of resistance to chemotherapeutic agents...
  45. Chromosome breakage and DNA detection in Tetrahymena
    Meng Chao Yao; Fiscal Year: 2006
    ..the somatic genome of this organism is dramatically re-structured during development through two processes: chromosome breakage and DNA deletion...
  46. TRI-NUCLEOTIDE REPEAT AND FRAGILE SITES IN YEAST
    Virginia Zakian; Fiscal Year: 2002
    ..b>Chromosome breakage at fragile site is also implicated in the chromosomal rearrangements characteristic of human tumors...
  47. GENETIC STUDIES WITH CULTIVATED MAMMALIAN CELLS
    ROBERT DE MARS; Fiscal Year: 1990
    ..system will have unusual capabilities for detecting agents and conditions that promote non-disjunction and chromosome breakage, both of which contribute to congenital abnormalities and cancer causation...
  48. CELL CULTURE-BASED STUDIES OF HCV PATHOGENESIS
    Michael Lai; Fiscal Year: 2007
    ..These include iNOS induction, double-strand DNA breaks, and induction of error-prone DNA polymerases. The possible involvement of extracellular E2 protein in causing these effects will also be examined. ..
  49. Mechanism of the RecBCD Enzyme from E. coli
    DOUGLAS JULIN; Fiscal Year: 2005
    ....
  50. ANALYSIS OF 8P LOSS IN HUMAN PROSTATE CANCER
    Jill Macoska; Fiscal Year: 2004
    ..This work should identify TSGs critical for prostate tumorigenesis mapping to proximal 8p and provide a basis for understanding their biological functions and their role(s) in malignant transformation and progression. ..
  51. GENESIS OF CHROMOSOMAL TRANSLOCATIONS
    Abram Gabriel; Fiscal Year: 2001
    ..e. R01) funding in the future. ..
  52. Cis-and trans-acting determinants of replication timing
    Joel Huberman; Fiscal Year: 2006
    ..Among the mechanisms causing genomic instability are chromosome breakage, gene amplification, and changes in levels of gene expression...
  53. The role of CENP-A in mammalian centromere specification
    DANIEL FOLTZ; Fiscal Year: 2005
    ..Specific Aim3: Finally, the studies proposed here are designed to determine whether CENP-A itself is sufficient to recruit centromere components and ultimately specify the centromere. ..
  54. CIS-ACTING DETERMINANTS OF REPLICATION TIMING
    Joel Huberman; Fiscal Year: 2001
    ..Among the mechanisms causing genomic instability are chromosome breakage, gene amplification, and changes in levels of gene expression...
  55. MOLECULAR/CYTOGENETICS--ESTROGEN INDUCED RENAL NEOPLASIA
    Jonathan Li; Fiscal Year: 2000
    ..g., breast and uterine tumor models) and contribute importantly to our understanding of the etiology of E-associated human cancers. ..
  56. THE NATURE OF RADIATION INDUCED GENETIC DAMAGE
    Edward Novitski; Fiscal Year: 1980
    ..The significance, both biological and statistical, of these observations is being pursued. ..
  57. MOLECULAR ANALYSIS OF THE BLOOMS SYNDROME GENE PRODUCT
    James German; Fiscal Year: 1999
    ..The PI's work will constitute the first steps toward elucidating the role of the BLM gene product in maintaining genetic fidelity in human somatic cells and how its mutation leads to the clinical phenotype of Bloom's Syndrome. ..
  58. ALTERATIONS IN THE PITSLRE PROTEIN KINASE IN MELANOMA
    Mark Nelson; Fiscal Year: 2000
    ....
  59. MUTATION IN HYBRIDS OF DROSOPHILA
    Michael Simmons; Fiscal Year: 2000
    ..The traits of this syndrome include an elevated mutation rate, frequent chromosome breakage, segregation distortion and sterility...
  60. Mechanism of break-induced replication in yeast
    Anna Malkova; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  61. NIH Director's Pioneer Award
    Titia de Lange; Fiscal Year: 2009
    ..kinases, such as ATM, ATR, Chk1, and Chk2, that emerged from genetic screens in yeast and studies of human chromosome breakage syndromes...
  62. MOLECULAR GENETIC ANALYSIS OF MAMMALIAN DNA REPLICATION
    Geoffrey Wahl; Fiscal Year: 2004
    ..Cells with such mutations have an increased frequency of chromosome breakage, and spawn the genetic variants that fuel cancer progression...
  63. Role of SMC1 Phosphorylation in Radiation Responses
    MICHAEL BARRY KASTAN; Fiscal Year: 2010
    ..These studies will help us understand how cells respond to DNA damage and other stresses at the molecular level. ..
  64. Molecular Biomarkers as Predictors of Hodgkin's Disease
    Randa El Zein; Fiscal Year: 2007
    ..The high risk population can be targeted for intensive preventive and early detection strategies. ..