权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

THEORETICAL ANALYSIS OF DNA SUPERHELICAL EQUILIBRIA

DNA超螺旋平衡的理论分析

基本信息

批准号：
6018880
负责人：
CRAIG J. BENHAM
金额：
$ 16.79万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-08-01 至 2001-07-31
项目状态：
已结题

项目摘要

This research program will apply the theoretical methods previously developed by this investigator to the analysis of strand separation in superhelical genomic DNA sequences. The strong associations previously found between sites of stress-induced duplex destabilization (SIDD) and specific types of regulatory regions will be investigated thoroughly. Many additional DNA sequences will be analyzed to determine the SIDD properties associated to transcriptionally active regions, replication origins, centromeres, mutational hotspots, chromosomal breakpoints and other sites of biological activity. The statistical significance of each association will be assessed. The present theoretical methods will be extended to treat the following cases not currently amenable to analysis: 1) long DNAs in which the topological coupling induced by superhelicity may be limited by nucleosomal winding, 2) duplex destabilization induced by the proximal binding of molecules such as transcription factors, 3) effects on transition behavior of local sequence modifications such as methylated or mispaired bases, or abasic sites, and 4) competitions between denaturation and other transitions to which specific local DNA sequences are susceptible, such as cruciform extrusion or transition to Z- or to H-form. Monte Carlo methods will be used to analyze the stabilization of B-form DNA at high temperatures by positive supercoiling. The existing collaboration with Dr. Richard Fye, which focuses on the development of theoretical methods to analyze DNA superhelical equilibria, will be continued. Collaborations with two experimental groups, will investigate the thermodynamics of superhelical DNA conformational transitions, and the roles they play in transcription.

本研究计划将应用先前的理论方法由该研究人员开发用于分析链分离超螺旋基因组DNA序列。之前的强关联发现在应力诱导双链体不稳定（SIDD）位点和对特定类型的监管区域进行深入调查。许多额外的 DNA 序列将被分析以确定 SIDD 与转录活性区域、复制相关的特性起源、着丝粒、突变热点、染色体断点和其他生物活性位点。每个的统计显着性协会将被评估。目前的理论方法将是扩展到治疗目前无法分析的以下病例： 1）长DNA，其中由超螺旋引起的拓扑耦合可能受到核小体缠绕的限制，2) 诱导的双链体不稳定通过转录因子等分子的近端结合，3) 对局部序列修饰的转换行为的影响，例如甲基化或错配碱基，或无碱基位点，以及 4) 竞争变性和其他转变之间的特定局部DNA 序列是敏感的，例如十字形挤出或过渡 Z-或H-形式。蒙特卡罗方法将用于分析 B 型 DNA 在高温下的稳定性超螺旋。与 Richard Fye 博士的现有合作，专注于 DNA 分析理论方法的发展超螺旋平衡，将继续。与两人合作实验小组将研究超螺旋的热力学 DNA 构象转变及其在转录中发挥的作用。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hen's teeth and whale's feet: generalized characters and their compatibility.

DOI：
10.1089/cmb.1995.2.515
发表时间：
1995-01-01
期刊：
Journal of computational biology : a journal of computational molecular cell biology
影响因子：
0
作者：
Benham, C;Kannan, S;Warnow, T
通讯作者：
Warnow, T

Development of ribozymes that target stathmin, a major regulator of the mitotic spindle.

开发针对有丝分裂纺锤体主要调节因子 Stathmin 的核酶。