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Regulation Analysis of DNA G-quadruplex and i-Motif by Single-Molecule Laser Tweezers

Cui, Yunxi
http://rave.ohiolink.edu/etdc/view?acc_num=kent1480231076937581

Abstract Details

2016, PHD, Kent State University, College of Arts and Sciences / Department of Chemistry and Biochemistry.
DNA tetraplexes, e.g., G-quadruplex and i-motif, play significant roles in the regulation of gene transcription. Such tetraplex structures are found in gene promoters. In addition, recent reports indicated that the two tetraplex structures can have conflicting biological activities. However, the equilibrium between the structures, which is important to fully understand the regulated mechanism, is still insufficiently studied. With laser tweezers based single molecule analysis, we first investigated the equilibrium among different i-motif structures and hairpin species in a cytosine (C)-rich bcl-2 promoter sequence. We established a novel molecular population dynamics method to describe the equilibrium. In the following, we found the effect of small modulators, such as ligand IMC-76, IMC-48 and protein hnRNP LL, on this equilibrium. Moreover, we expended the molecular population dynamic method to other systems and showed the wide applicability of this method. In duplex DNA, we also introduced a population-based method to analyze the G-quadruplex and i-motif which locate in the complementary strands. Our result revealed that the two tetraplex structures were mutually exclusive in a variety of DNA templates, which include human telomere and promoter fragments of hINS and hTERT genes. In addition, we found that mutual exclusivity between the two tetraplex structures was controlled by steric hindrance. Our discovery provides explanations to the mechanisms of gene expression regulated by tetraplex structures. The insights into the mechanisms will provide new therapeutic strategies against G-quadruplex and i-motif related diseases, such as cancers and Parkinson’s.
Hanbin Mao (Advisor)
Songping Huang (Committee Member)
Anatoly Khitrin (Committee Member)
Qi-Huo Wei (Committee Member)
110 p.
Analytical Chemistry; Biochemistry
Laser tweezers; Single molecule; DNA

Recommended Citations

Citations

  • Cui, Y. (2016). Regulation Analysis of DNA G-quadruplex and i-Motif by Single-Molecule Laser Tweezers [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1480231076937581

    APA Style (7th edition)

  • Cui, Yunxi. Regulation Analysis of DNA G-quadruplex and i-Motif by Single-Molecule Laser Tweezers. 2016. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1480231076937581.

    MLA Style (8th edition)

  • Cui, Yunxi. "Regulation Analysis of DNA G-quadruplex and i-Motif by Single-Molecule Laser Tweezers." Doctoral dissertation, Kent State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1480231076937581

    Chicago Manual of Style (17th edition)

kent1480231076937581
786
© 2016, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.