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Title: Quadruplex folding within double helical segments of gene regulatory regions
Author: Lam, Wan Chi
ISNI:       0000 0004 2720 2198
Awarding Body: University of Ulster
Current Institution: Ulster University
Date of Award: 2010
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Gene regulatory regions, such as promoters or introns in the human genome, are rich in putative quadruplex forming sequences. G-quadruplex formation in these duplex regions requires the opening of duplex so that the single stranded region can fold into a G-quadruplex. The factors that affect the transition of duplex to G- quadruplex are currently not well understood. In this dissertation, we show that the availability of fragile sites, percentual GC content of the flanking sequence, loop composition, and loop-length, are all determinant factors for G-quadruplex formation within the native double helical segments. These factors are introduced and discussed in the first Chapter. In the following Chapters, 2 through 5, we investigate the propensity for formation of G-quadruplex topologies within the proximal promoter region of SRC, FGF2, and MYCN, as well as the first intron of IGF2. Except for MYCN we were able to establish formation of parallel quadruplexes from within the native double helical segments. We were not able to conclude on formation of a quadruplex in MYCN; even though there is evidence that a DNA higher order architecture forms. Significantly, the investigated guanine-rich segment of the proximal promoter of FGF2 gene shows propensity to fold into the parallel stranded quadruplex in the absence of crowding agents. In the final Chapter (6) these findings are discussed in the context of the factors that allow for the transition from closed to open double helix, and formation and stability of the parallel stranded quadruplexes. Finally, in this Chapter the biological significance of finding parallel stranded quadruplexes in this set of genes is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available