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  • 1
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    Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-01-06
    Description: Interactions between ends from different DNA double-strand breaks (DSBs) can produce tumorigenic chromosome translocations. Two theories for the juxta-position of DSBs in translocations, the static "contact-first" and the dynamic "breakage-first" theory, differ fundamentally in their requirement for DSB mobility. To determine whether or not DSB-containing chromosome domains are mobile and can interact, we introduced linear tracks of DSBs in nuclei. We observed changes in track morphology within minutes after DSB induction, indicating movement of the domains. In a subpopulation of cells, the domains clustered. Juxtaposition of different DSB-containing chromosome domains through clustering, which was most extensive in G1 phase cells, suggests an adhesion process in which we implicate the Mre11 complex. Our results support the breakage-first theory to explain the origin of chromosomal translocations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aten, Jacob A -- Stap, Jan -- Krawczyk, Przemek M -- van Oven, Carel H -- Hoebe, Ron A -- Essers, Jeroen -- Kanaar, Roland -- New York, N.Y. -- Science. 2004 Jan 2;303(5654):92-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Microscopical Research, Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14704429" target="_blank"〉PubMed〈/a〉
    Keywords: Alpha Particles ; Animals ; Ataxia Telangiectasia/genetics/metabolism ; CHO Cells ; Cell Nucleus/metabolism/radiation effects ; *Chromosome Breakage ; Chromosomes, Human/*metabolism ; Chromosomes, Mammalian/metabolism ; Cricetinae ; Cricetulus ; DNA/*metabolism/radiation effects ; *DNA Damage ; DNA Repair ; DNA-Binding Proteins/metabolism ; Fibroblasts/metabolism ; G1 Phase ; G2 Phase ; HeLa Cells ; Histones/*metabolism ; Humans ; Phosphorylation ; Rad51 Recombinase ; S Phase ; Translocation, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Involvement of mammalian Mus81 in genome integrity and tumor suppression (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-06-19
    Description: Mus81-Eme1 endonuclease has been implicated in the rescue of stalled replication forks and the resolution of meiotic recombination intermediates in yeast. We used gene targeting to study the physiological requirements of Mus81 in mammals. Mus81-/- mice are viable and fertile, which indicates that mammalian Mus81 is not essential for recombination processes associated with meiosis. Mus81-deficient mice and cells were hypersensitive to the DNA cross-linking agent mitomycin C but not to gamma-irradiation. Remarkably, both homozygous Mus81-/- and heterozygous Mus81+/- mice exhibited a similar susceptibility to spontaneous chromosomal damage and a profound and equivalent predisposition to lymphomas and other cancers. These studies demonstrate a critical role for the proper biallelic expression of the mammalian Mus81 in the maintenance of genomic integrity and tumor suppression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McPherson, John Peter -- Lemmers, Benedicte -- Chahwan, Richard -- Pamidi, Ashwin -- Migon, Eva -- Matysiak-Zablocki, Elzbieta -- Moynahan, Mary Ellen -- Essers, Jeroen -- Hanada, Katsuhiro -- Poonepalli, Anuradha -- Sanchez-Sweatman, Otto -- Khokha, Rama -- Kanaar, Roland -- Jasin, Maria -- Hande, M Prakash -- Hakem, Razqallah -- New York, N.Y. -- Science. 2004 Jun 18;304(5678):1822-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ontario Cancer Institute, 620 University Avenue, Suite 706, Toronto, Ontario, Canada M5G 2C1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15205536" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Chromosome Aberrations ; DNA Damage ; DNA-Binding Proteins/*genetics/*physiology ; Embryo, Mammalian/cytology ; Embryonic and Fetal Development ; *Endonucleases ; Gamma Rays ; Gene Targeting ; Genetic Predisposition to Disease ; *Genome ; *Genomic Instability ; Heterozygote ; Lymphoma/etiology/genetics/pathology ; Meiosis ; Mice ; Mitomycin/pharmacology ; Neoplasms/etiology/*genetics ; Recombination, Genetic ; Saccharomyces cerevisiae Proteins ; Sister Chromatid Exchange ; Stem Cells ; T-Lymphocytes/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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