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Title: Biophysical studies on DNA micromechanics and bacterial nucleoid organization
Keywords: DNA overstretching; MD simulation; kinetic simulation; MTB Lsr2; magnetic tweezers;DNA organization
Issue Date: 14-Aug-2013
Citation: QU YUANYUAN (2013-08-14). Biophysical studies on DNA micromechanics and bacterial nucleoid organization. ScholarBank@NUS Repository.
Abstract: My Ph.D research focused on two topics: force-induced DNA structural transitions, and the interaction between DNA and the Mycobacterium tuberculosis protein Lsr2. These studies involved extensive theoretical and experimental approaches, which addressed several outstanding questions in the field. I theoretically investigated the stability of different force-induced DNA structures identified in recent experiments, and elucidated the kinetics of their transitions from one to another. Further, using a novel steered full-atom molecular dynamics simulation strategy, an elongated double-stranded DNA structure was produced, which is a possible candidate for the mysterious S-DNA structure proposed recently. On Lsr2-DNA interaction, I found that Lsr2 cooperatively binds to DNA and forms a rigid Lsr2 nucleoprotein complex at a single DNA level, which restricts DNA accessibility and also mediate tight DNA condensation. These results provide mechanistic insights into the two functions of Lsr2, namely gene silencing by DNA access restriction, and genomic DNA packaging by DNA condensation.
Appears in Collections:Ph.D Theses (Open)

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