• Login
    View Item 
    •   SMARTech Home
    • Georgia Tech Theses and Dissertations
    • Georgia Tech Theses and Dissertations
    • View Item
    •   SMARTech Home
    • Georgia Tech Theses and Dissertations
    • Georgia Tech Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Mechanisms of chromosomal instability induced by unstable DNA repeats in yeast S.cerevisiae

    Thumbnail
    View/Open
    ZHANG-DISSERTATION-2013.pdf (2.885Mb)
    Date
    2013-06-28
    Author
    Zhang, Yu
    Metadata
    Show full item record
    Abstract
    DNA repetitive sequences capable of adopting non-B DNA structures are a potent source of instability in eukaryotic genomes. They are strong inducers of chromosomal fragility and genome rearrangements that cause various hereditary diseases and cancers. In addition, a subset of repeats also has an ability to expand, which leads to more than 20 human genetic diseases that are collectively known as repeat expansion diseases. However, the mechanisms underlying the potential of these structure-prone motifs to break and expand are largely unknown. In this study, a systematic genome-wide screen was employed in yeast Saccharomyces cerevisiae to investigate the contributing factors of the instability of two representative non-B DNA-forming repeats: the triplex-adopting GAA/TTC tracts and the inverted repeats that can form hairpin and cruciform structures. The GAA/TTC screen revealed that DNA replication and transcription initiation are the two major pathways governing the GAA/TTC stability in yeast, as corresponding mutants strongly induce both fragility and large-scale expansions of the repeats. The inverted repeats screen and follow-up experiments revealed that both replication-dependent and -independent pathways are involved in maintaining the stability of palindromic sequences. We propose that similar mechanisms could operate in the human cells to mediate the deleterious metabolism of GAA and inverted repeats.
    URI
    http://hdl.handle.net/1853/52185
    Collections
    • Georgia Tech Theses and Dissertations [22398]
    • School of Biology Theses and Dissertations [410]

    Browse

    All of SMARTechCommunities & CollectionsDatesAuthorsTitlesSubjectsTypesThis CollectionDatesAuthorsTitlesSubjectsTypes

    My SMARTech

    Login

    Statistics

    View Usage StatisticsView Google Analytics Statistics
    • About
    • Terms of Use
    • Contact Us
    • Emergency Information
    • Legal & Privacy Information
    • Accessibility
    • Accountability
    • Accreditation
    • Employment
    • Login
    Georgia Tech

    © Georgia Institute of Technology

    • About
    • Terms of Use
    • Contact Us
    • Emergency Information
    • Legal & Privacy Information
    • Accessibility
    • Accountability
    • Accreditation
    • Employment
    • Login
    Georgia Tech

    © Georgia Institute of Technology