The Topology and Geometry of Intrinsically Bent DNA

本质弯曲 DNA 的拓扑和几何结构

• 批准号: 9805142
• 负责人: James White
• 金额: $ 8.7万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9805142&HistoricalAwards=false
• 关键词: Topology; Geometry; Intrinsically; Bent; DNA

White9805142 The investigator studies the structure of closed circularDNA. The theoretical approach employs displacement-based FiniteElement Analysis (FEA), a well-established technique forobtaining solutions to engineering problems in nonlinear solidmechanics. FEA is used to describe closed DNAs containingmultiple coplanar bends that are in-phase; containing bends thatdo not lie in the same plane; and containing bends distributedboth symmetrically and asymmetrically. It is predicted that thetwist distribution is uniform throughout the regions between thebends; that the fraction of the linking number change convertedinto writhe increases with the number of bends; and that theregional contribution to the writhe increases if the bends areclustered in that region. Finally, it is predicted that theequilibrium configurations of DNA containing multiple bends fallinto two distinct classes of writhe behavior, depending on theratio of the elastic moduli and the number of bends, and that theinitial supercoiling process is completely different for the twodifferent classes. Biologically, closed circular DNA is one ofthe most important structural forms of DNA. This includes notonly free DNA molecules, such as the plasmids used in all geneticengineering experiments, but chromatin as well, which is nowknown to be divided into domains of supercoiling. Bent regionsin DNA appear to be significant in regulating the initiating oftranscription. This project provides the physical basis forunderstanding the combined effects of these two structures. DNA not only is a repository for genetic information butalso is involved in many aspects of the expression of thisinformation. For example, it is often necessary to bringtogether portions of the DNA molecule that lie at considerabledistances from each other along the DNA contour. Thisjuxtaposition of distant genetic elements makes possible theexpression of biological information that is not otherwisepossible. This process is accomplished by forming a loop, inwhich the two elements that are to be brought together interactat the site of loop closure. The bringing together of thesedistant genes depends in a sensitive way upon the length of theDNA piece that separates them, upon the helical periodicity, andupon the salt concentration of the cell in which the DNA resides.This project shows how the presence of internal bends in DNAwithin the loop fundamentally changes how distant segments arebrought together. The distribution of these internal bends canthus have profound biological consequences.

White9805142研究者研究了封闭环的结构。 理论方法采用基于流离失所的有限元分析（FEA），这是一种良好的技术，可以实现非线性固体机力学工程问题的解决方案。 FEA用于描述含有相相的封闭的DNA含有的Coclanar弯曲；包含不在同一平面上的弯曲；并包含弯曲的弯曲，对称和不对称。 据预测，在倾向之间的整个区域中，thetwist的分布是统一的。链接数的比例变化转化为扭曲的扭曲随弯曲的数量增加。如果弯曲在该区域占据，则对扭动的贡献会增加。 最后，可以预测，含有多个弯曲的DNA的平衡构型取决于弹性模量和弯曲的数量，而两种弯曲的行为的不同类别，而二分类别的弯曲构造则完全不同。 在生物学上，闭合的圆形DNA是最重要的DNA结构形式之一。 这包括非遗传性DNA分子，例如所有遗传性实验实验中使用的质粒，但也包括染色质，现在众所周知，该质粒被划分为超涂层的域。 弯曲区域中的DNA似乎在调节转录的启动时很重要。 该项目为这两种结构的综合效应提供了物理基础。 DNA不仅是遗传信息的存储库，而且还参与了该信息表达的许多方面。 例如，通常有必要将沿DNA轮廓彼此的Avidabledistances置于DNA分子的部分。 遥远的遗传元素的生存使生物信息的表达可能是不可超越的。 通过形成循环来实现此过程，这两个要素将互动的两个元素互动。 这些基因的结合以一种敏感的方式取决于将其分开的螺旋周期性分离的thedna片段的长度，以及DNA所居住的细胞的盐浓度。该项目显示了dnawithin中内部弯曲的存在如何从根本上改变了循环的根本性改变了分散段的偏移段。 这些内部弯曲的分布会产生深远的生物学后果。