DNA BENDING IN TRANSCRIPTION INITIATION
DNA BENDING IN TRANSCRIPTION INITIATION
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DOI：
10.1101/sqb.1993.058.01.015
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发表时间：
1993-01-01
期刊：
影响因子：
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通讯作者：
CROTHERS, DM
中科院分区：
文献类型：
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作者：
KAHN, JD;CROTHERS, DM
DNA螺旋只有在理想条件下才是直的。弯曲或弯曲可以由热作用力下的弯曲、特殊的序列模式（如重复的A束）和结合蛋白或其他配体引起的应力引起。所有这些都导致DNA在细胞内弯曲，但体内的主要致病机制是蛋白质诱导的弯曲，例如，由核心组蛋白产生多核体纤维。调控蛋白在转录起始位点之前的启动子序列等位点引起DNA弯曲也是常见的。事实上，需要DNA解绕的转录和复制等过程的起始似乎是一个一般规则，在解绕点远端的DNA弯曲之前。这种概括的物理基础还有待阐明。DNA弯曲影响调节现象的一个简单机制是通过两种或两种以上蛋白质结合的协同作用，因为它们对弯曲的DNA有共同的偏好。例如，如果RNA聚合酶周围的DNA弯曲或环化伴随着转录起始，那么来自大肠杆菌的camp结合蛋白（CAP或CRP）等激活蛋白可以弯曲DNA (Wu and Crothers 1984; Schultz et al. 1991)，可以与聚合酶共享产生必要弯曲的工作。通过这种方式，蛋白质可以协同或协同作用，而不必相互接触。这里报告的工作的目的是探讨这种合作的物质基础。
The DNA helix is straight only under idealized conditions. Bends or curvature can result from flexing under thermal forces, from special sequence patterns such as repeated A tracts, and from stress induced by binding proteins or other ligands. All of these cause DNA to bend in cells, but the chief causative mechanism in vivo is protein-induced bending, for example, by core histones to produce polynucleosomal fibers. It is also common for regulatory proteins to cause DNA bending at loci such as the promoter sequences preceding transcription start sites. Indeed, it seems to be a general rule that initiation of processes such as transcription and replication that require DNA unwinding is preceded by DNA bending at a site distal to the point of unwinding. The physical basis for this generalization remains to be elucidated.One simple mechanism by which DNA bending can influence regulatory phenomena is through synergy in the binding of two or more proteins because they share a preference for bent DNA. For example, if bending or looping of DNA around RNA polymerase accompanies transcription initiation, then an activating protein like the cAMP-binding protein (CAP or CRP) from Escherichia coli, which is known to bend DNA (Wu and Crothers 1984; Schultz et al. 1991), can share with polymerase the work of producing the necessary bend. In this way proteins can act synergistically or cooperatively, without necessarily having to be in contact. The objective of the work reported here is to explore the physical basis for this kind of cooperativity.