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  • 1
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    Strand-specific postreplicative processing of mammalian telomeres (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-09-29
    Description: Telomeres are specialized nucleoprotein structures that stabilize the ends of linear eukaryotic chromosomes. In mammalian cells, abrogation of telomeric repeat binding factor TRF2 or DNA-dependent protein kinase (DNA-PK) activity causes end-to-end chromosomal fusion, thus establishing an essential role for these proteins in telomere function. Here we show that TRF2-mediated end-capping occurs after telomere replication. The postreplicative requirement for TRF2 and DNA-PKcs, the catalytic subunit of DNA-PK, is confined to only half of the telomeres, namely, those that were produced by leading-strand DNA synthesis. These results demonstrate a crucial difference in postreplicative processing of telomeres that is linked to their mode of replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bailey, S M -- Cornforth, M N -- Kurimasa, A -- Chen, D J -- Goodwin, E H -- AG-917709/AG/NIA NIH HHS/ -- CA50519/CA/NCI NIH HHS/ -- CA76260/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Sep 28;293(5539):2462-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11577237" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Line ; Chromatids/physiology/ultrastructure ; Chromosomes/physiology/ultrastructure ; *DNA Replication ; DNA-Activated Protein Kinase ; DNA-Binding Proteins/genetics/*metabolism ; Humans ; In Situ Hybridization ; Mice ; Mitosis ; Mutation ; Nuclear Proteins ; Protein-Serine-Threonine Kinases/deficiency/metabolism ; Telomere/*metabolism ; Telomeric Repeat Binding Protein 2 ; Tumor Cells, Cultured
    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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    X-ray--induced breakage and rejoining of human interphase chromosomes (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-12-09
    Description: A method was developed for the high-resolution measurement of breaks in prematurely condensed chromosomes at the G1 phase of the cell cycle. The dose response for fragments (breaks) produced immediately after x-irradiation of confluent cultures of normal human cells was linear down to 10.9 rad (0.109 Gy) and extrapolated to zero effect at zero dose. The curve had a slope of 0.063 breaks per cell per rad, which is at least an order of magnitude greater than that for breaks scored in the same cells after they have progressed to mitosis following subculture. When incubated at 37 degrees C half of the breaks disappeared in 2 hours. A slower, perhaps nonrejoining component was apparent at later incubation times. The initial rate of break rejoining was similar to the rate of increase in survival after incubation because of the repair of potentially lethal damage and is also in close agreement with recently reported values for the rejoining of double-strand breakage in DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cornforth, M N -- Bedford, J S -- CA 18023/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1983 Dec 9;222(4628):1141-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6648528" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosome Aberrations ; Chromosomes, Human/*radiation effects/ultrastructure ; Dose-Response Relationship, Radiation ; Humans ; Hybrid Cells/ultrastructure ; Interphase ; Mitosis ; Mutation/*radiation effects ; X-Rays
    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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  • 3
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    On the nature of a defect in cells from individuals with ataxia-telangiectasia (1985)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1985-03-29
    Description: The cells and tissues of patients with ataxia-telangiectasia (A-T), an inherited disease characterized by a high degree of proneness to cancer, are abnormally sensitive to ionizing radiation. Noncycling cultures of normal human and A-T fibroblasts were exposed to x-rays so that the breakage and rejoining of prematurely condensed chromosomes in the G1 phase could be compared. After a dose of 6.0 grays, both cell types had the same initial frequency of breaks and the same rate for rejoining of the breaks, but the fraction of breaks that did not rejoin was five to six times greater for the A-T cells. The results also show that progression of cells into the S phase is not a prerequisite for the increased frequency of chromosome fragments that appear in mitosis after A-T cells are irradiated in the G1 or G0 phase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cornforth, M N -- Bedford, J S -- CA 18023/CA/NCI NIH HHS/ -- CA 36447/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1985 Mar 29;227(4694):1589-91.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3975628" target="_blank"〉PubMed〈/a〉
    Keywords: Ataxia Telangiectasia/*genetics ; Cells, Cultured ; Chromatin/radiation effects ; Chromosome Aberrations ; Chromosomes, Human/radiation effects ; DNA/radiation effects ; Humans ; X-Rays
    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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  • 4
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    Asynchronous replication timing of telomeres at opposite arms of mammalian chromosomes (2004)
    National Academy of Sciences
    Details
    Publication Date: 2004-08-20
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    Telomeres and DNA double-strand breaks: ever the twain shall meet? (2007)
    Springer
    Details
    Publication Date: 2007-09-18
    Print ISSN: 1420-682X
    Electronic ISSN: 1420-9071
    Topics: Biology , Medicine
    Published by Springer
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  • 6
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    Termini of human chromosomes display elevated rates of mitotic recombination (2001)
    Oxford University Press
    Details
    Publication Date: 2001-01-01
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white (1997)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: Genomic instability has been proposed to be the earliest step in radiation-induced tumorigenesis. It follows from this hypothesis that individuals highly susceptible to induction of tumors by radiation should exhibit enhanced radiation-induced instability. BALB/c white mice are considerably more sensitive to radiation-induced mammary cancer than C57BL/6 black mice. In this study, primary mammary epithelial cell cultures from these two strains were examined for the "delayed" appearance of chromosomal aberrations after exposure to 137Cs gamma radiation, as a measure of radiation-induced genomic instability. As expected, actively dividing cultures from both strains showed a rapid decline of initial asymmetrical aberrations with time postirradiation. However, after 16 population doublings, cells from BALB/c mice exhibited a marked increase in the frequency of chromatid-type breaks and gaps which remained elevated throughout the time course of the experiment (28 doublings). No such effect was observed for the cells of C57BL/6 mice; after the rapid clearance of initial aberrations, the frequency of chromatid-type aberrations in the irradiated population remained at or near those of nonirradiated controls. These results demonstrate a correlation between the latent expression of chromosomal damage in vitro and susceptibility for mammary tumors, and provide further support for the central role of radiation-induced instability in the process of tumorigenesis.
    Keywords: Aerospace Medicine
    Type: Radiation research (ISSN 0033-7587); 147; 2; 121-5
    Format: text
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    NASA TECHNICAL REPORTS
  • 8
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    Overview of NASARTI (NASA Radiation Track Image) Program: Highlights of the Model Improvement and the New Results (2014)
    In:  CASI
    Details
    Publication Date: 2019-07-19
    Description: This presentation summarizes several years of research done by the co-authors developing the NASARTI (NASA Radiation Track Image) program and supporting it with scientific data. The goal of the program is to support NASA mission to achieve a safe space travel for humans despite the perils of space radiation. The program focuses on selected topics in radiation biology that were deemed important throughout this period of time, both for the NASA human space flight program and to academic radiation research. Besides scientific support to develop strategies protecting humans against an exposure to deep space radiation during space missions, and understanding health effects from space radiation on astronauts, other important ramifications of the ionizing radiation were studied with the applicability to greater human needs: understanding the origins of cancer, the impact on human genome, and the application of computer technology to biological research addressing the health of general population. The models under NASARTI project include: the general properties of ionizing radiation, such as particular track structure, the effects of radiation on human DNA, visualization and the statistical properties of DSBs (DNA double-strand breaks), DNA damage and repair pathways models and cell phenotypes, chromosomal aberrations, microscopy data analysis and the application to human tissue damage and cancer models. The development of the GUI and the interactive website, as deliverables to NASA operations teams and tools for a broader research community, is discussed. Most recent findings in the area of chromosomal aberrations and the application of the stochastic track structure are also presented.
    Keywords: Life Sciences (General); Space Radiation; Aerospace Medicine
    Type: JSC-CN-30136 , NASA Human Research Program Investigators'' Workshop; Feb 12, 2014 - Feb 13, 2014; Galveston, TX; United States
    Format: application/pdf
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    NASA TECHNICAL REPORTS
  • 9
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    Strand-Specific Postreplicative Processing of Mammalian Telomeres (2001)
    American Association for the Advancement of Science
    Details
    Publication Date: 2001-09-28
    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
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