Structural analysis of telomere binding factors and repetitive DNAs Public Deposited

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Last Modified
  • March 21, 2019
Creator
  • Fouché, Nicole
    • Affiliation: School of Medicine, Department of Biochemistry and Biophysics
Abstract
  • Telomeres are typically long nucleoprotein structures that protect the ends of linear chromosomes from exonucleolytic attack and from being recognized as DNA double strand breaks. Telomeric DNA is lost either gradually, as a consequence of cellular ageing, or sometimes rapidly, when the telomere structure is disrupted or due to errors in telomere maintenance. When greatly shortened, telomeres will signal a DNA damage message that results in an active growth arrest and eventually, cell death. Telomeres are thus molecular clocks that present a formidable barrier against cancer, because functional telomeres are essential for continued cell proliferation. Thus an important strategy for cancer therapeutics lies in understanding and targeting telomere-lengthening mechanisms used by cancer cells. However, telomere length is determined by the intricate interplay of the components that lengthen telomeres and those that shorten them. Therefore, a detailed understanding is also needed of the structures and functions of telomere factors present in normal cells, and of how changes in these can lead to cancer. Presented here are structural analyses of the telomeric DNA itself; the yeast RNA component of the telomere-lengthening protein, telomerase; and the DNA binding properties of telomerase and another telomere-specific protein, TRF2. Together, the data adds to a more comprehensive structural model for the manner in which telomeres function in vivo.
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  • In Copyright
Advisor
  • Griffith, Jack D.
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Open access
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