Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


Sangeetha-DissertationV2.pdf (7.76 MB)

ETD Abstract Container

Abstract Header

Molecular Population Dynamics of DNA Tetraplexes using Magneto-Optical Tweezers

Selvam, Sangeetha
http://orcid.org/0000-0002-3890-5126
http://rave.ohiolink.edu/etdc/view?acc_num=kent1516742116760289

Abstract Details

2018, PHD, Kent State University, College of Arts and Sciences / Department of Chemistry.
The most common B-form Deoxyribonucleic acid (DNA) consists of two polymeric nucleic acid chains held together by Watson-Crick base pair (bp) with a right-handed twist at every 10.5 bp. In the nucleus, the DNA is subjected to spatial constraint and hence undergoes supercoiling (σ) to relieve stress through either overwinding (positive superhelicity), unwinding (negative superhelicity), DNA bending or melting. Similar topological changes observed during many cellular processes such as transcription, replication, etc. have a significant effect on the rate of these processes. Apart from the duplex DNA, many other non-B DNA structures exist in cells such as hairpin, G-quadruplex, i-motif, triplex, cruciform, etc. There is a lack of information on the topology of these structures under torsional stress. My research work focused on addressing the population dynamics of non-B DNA tetraplex structures under torsionally constrained physiological conditions at the molecular level. For this study, we developed magneto-optical tweezers by combining dual-beam optical tweezers and the manipulation of magnetic tweezers for rotation. The effect of torsional stress on the topology of non-B DNA tetraplexes was studied by varying the superhelicity of the template DNA through rotation of the magnets. For this study, we analyzed the sequence [d(ACAGGGGTGTGGGG)2] from a promoter region of Insulin Linked Polymorphic Region and quantified the molecular population dynamics of DNA tetraplexes under various chemical (ions and pH) and mechanical (template superhelicity and molecular crowding) conditions by single-molecule mechanical unfolding methods. By mechanical unfolding of individual tetraplexes, we found that ions and pH have the most substantial effect on the formation of G-quadruplex and i-motif, respectively. Interestingly, superhelicity has the second largest effect followed by molecular crowding condition. While chemical effects are specific to tetraplex species mechanical factors show generic influences. This result provides substantial evidence for topology-based transcription modulation at the molecular level. Understanding the effect of torsional stress on the topology of secondary structures found in the chromosomes will serve as a deep insight into various cellular functions.
Hanbin Mao, PhD (Committee Chair)
Mietek Jaroniec, PhD (Committee Member)
Bansidhar Datta, PhD (Committee Member)
Elizabeth Mann, PhD (Committee Member)
Ernest Freeman, PhD (Committee Member)
137 p.
Analytical Chemistry; Biochemistry; Biophysics; Chemistry
DNA Supercoil; single-molecule; optical tweezers; magneto-optical tweezers; G-quadruplex; i-motif; torsionally constrained DNA;

Recommended Citations

Citations

  • Selvam, S. (2018). Molecular Population Dynamics of DNA Tetraplexes using Magneto-Optical Tweezers [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1516742116760289

    APA Style (7th edition)

  • Selvam, Sangeetha. Molecular Population Dynamics of DNA Tetraplexes using Magneto-Optical Tweezers. 2018. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1516742116760289.

    MLA Style (8th edition)

  • Selvam, Sangeetha. "Molecular Population Dynamics of DNA Tetraplexes using Magneto-Optical Tweezers." Doctoral dissertation, Kent State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1516742116760289

    Chicago Manual of Style (17th edition)

kent1516742116760289
317
© 2018, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.