How bacterial SMC complexes organize chromosomes

细菌 SMC 复合体如何组织染色体

基本信息

批准号：
10362622
负责人：
Xindan Wang
金额：
$ 33.54万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10362622
关键词：
ATP Hydrolysis ATP phosphohydrolase Address Bacillus subtilis Bacteria Bacterial Genome Binding Sites Cell Cycle Cells Chromatin Loop Chromosome Arm Chromosome Segregation Chromosome Structures Chromosomes Complex Cytology DNA DNA biosynthesis Data Engineering Eukaryota Exhibits Genetic Transcription Genome Genomics Goals Growth Head In Vitro Interphase Left Life Maintenance Measures Methods Modeling Molecular Organism Plasmids Play Polymers Process Proteins Reagent Replication Origin Replicon Reproductive Process Research Resolution Rhizobium radiobacter Rod Role Sister Sister Chromatid Site Structure System Tail Time Work base chromatin immunoprecipitation chromosome conformation capture cohesin condensin deep sequencing dimer experimental study genome integrity in vivo novel recombinase repaired segregation simulation single molecule time use tool

项目摘要

Project Summary The organization and segregation of replicated chromosomes are fundamental to living systems. Structural maintenance of chromosomes (SMC) complexes play central roles in these processes in all domains of life. These ring-shaped ATPases share common structures and inter-subunit contacts, consistent with a common mechanism of action. Over the last five years, studies in Bacillus subtilis and eukaryotes have provided compelling in vivo and in vitro evidence that SMC complexes utilize ATP hydrolysis to extrude DNA loops. In the case of B. subtilis, SMC condensin complexes are loaded at centromeric parS sites near the replication origin, then translocate down the left and right chromosome arms, tethering them together. In this way, condensins generate a single chromosome loop centered on the origin that draws sister chromosomes in on themselves and away from each other. This elegantly simple loop-extrusion model provides a unifying mechanism to explain how eukaryotic SMC cohesin complexes form topologically associating domains (TADs) in interphase, how eukaryotic SMC condensin complexes compact DNA into rod-shaped sister chromatids, and how bacterial SMC condensins resolve newly replicated origins. However, this model raises an important question: how do SMC complexes extrude DNA loops when the chromosome is coated by numerous proteins and acted upon by replication and transcription machineries? And how are the topologically loaded complexes released from the chromosome? The goal of this proposed research is to understand the mechanism of condensin action in the context of cellular activities, taking advantage of the many molecular and cytological tools we have developed. First, we will determine how condensins act when they encounter the replisome or other condensin molecules. Second, we will characterize how condensins are released from the chromosome when they reach the terminus region. Finally, we will explore condensin’s role in the organization and dynamics of a multipartite bacterial genome that contains both a circular and a linear chromosome. Taken together, the proposed work has the potential to provide the general principles of chromosome folding and compaction in all organisms.

项目概要复制染色体的组织和分离是生命系统的基础。染色体维护（SMC）复合体在生命各个领域的这些过程中发挥着核心作用。这些环状 ATP 酶具有共同的结构和亚基间接触，与共同的结构一致。在过去五年中，枯草芽孢杆菌和真核生物的研究提供了作用机制。令人信服的体内和体外证据表明 SMC 复合物利用 ATP 水解来挤出 DNA 环。对于枯草芽孢杆菌，SMC 凝缩蛋白复合物加载在靠近复制起点的着丝粒 parS 位点，然后沿着左右染色体臂向下移位，以这种方式将它们束缚在一起。生成以原点为中心的单个染色体环，将姐妹染色体吸引到自身中，并且这个优雅简单的循环挤压模型提供了一个统一的机制来解释如何相互远离。真核细胞 SMC 粘连蛋白复合物在间期形成拓扑关联结构域 (TAD)，真核细胞如何 SMC 凝缩蛋白复合物将 DNA 压缩成杆状姐妹染色单体，以及细菌 SMC 凝缩蛋白的原理然而，这个模型提出了一个重要的问题：SMC复合体是如何进行的。当染色体被大量蛋白质包裹并受到复制和作用时，挤出 DNA 环转录机制？拓扑负载复合物是如何从染色体中释放出来的？这项研究的目的是了解细胞中凝缩蛋白的作用机制活动，利用我们开发的许多分子和细胞学工具。确定凝缩蛋白在遇到复制体或其他凝缩蛋白分子时如何起作用。将描述凝缩蛋白到达末端区域时如何从染色体中释放的特征。最后，我们将探讨凝缩蛋白在多部分细菌基因组的组织和动态中的作用，综合起来，这项工作有可能提供环状和线性染色体。所有生物体中染色体折叠和压缩的一般原理。