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The Physics of Target-site Search and DNA Supercoiling in the Cell

出版	Stanford University, 2012
URL	http://books.google.com.hk/books?id=F_GWnQAACAAJ&hl=&source=gbs_api

註釋Protein-DNA interactions within the confines of the crowded cellular space control critical biological processes such as genome regulation, replication, and compaction. In turn, protein activity on the genome is susceptible to the structure and dynamics of the DNA itself, a complex relationship whose study falls within the realm of polymer physics. Using analytical theory and numerical simulations, we present a systematic study of the relationship between DNA structure and dynamics and cellular processes mediated by DNA-binding proteins, in particular those involving a search for a target-site on the chromosome. We build a theoretical description of the transport of DNA-binding proteins along linear DNA modeled as a wormlike chain and delineate the resulting dynamic strategies employed by the cell in order to maximize translocation speed and efficiency. We extend this model to address the otherwise imperceptible molecular events present during effective protein diffusion along a stretched DNA strand during single-molecule experiments. In an effort to address the genome's higher-order structural effects, we explore the structure and dynamics of supercoiled DNA both as a free molecule in solution and under confinement in the cell, as in the case of Caulobacter crescentus. Our investigation of supercoiled DNA in confinement highlights dynamic consequences of vital importance to the cell's genome regulatory strategies. Finally, we synthesize our study of DNA-binding protein transport with our investigation of supercoiling dynamics to address the effect of DNA superstructure on the target-site search process, and we identify the search enhancement wrought by supercoiling of the chromosome.