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：
10594399
负责人：
Xindan Wang
金额：
$ 33.19万
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/10594399
关键词：
ATP Hydrolysis ATP phosphohydrolase Address Bacillus subtilis Bacteria Bacterial Genome Binding 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 Shapes Sister Sister Chromatid Site Structure System Tail Time Work chromatin immunoprecipitation chromosome conformation capture chromosome replication 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.

项目摘要复制的染色体的组织和隔离是生物系统的基础。结构维持染色体（SMC）复合物在生活的所有领域的这些过程中都起着核心作用。这些环形ATPases共享共同的结构和育间接触，与共同作用机理。在过去的五年中，枯草芽孢杆菌和真核生物的研究提供了诱人的体内和体外证据表明，SMC复合物利用ATP水解挤出了DNA环。在枯草芽孢杆菌的病例，SMC冷凝蛋白复合物在复制起源附近的中心层面位点加载然后将左右染色体臂置于旋转，将它们绑在一起。这样，冷凝剂产生一个以染色体为中心的染色体循环，该起源吸引了姐妹染色体，并彼此远离。这个优雅的简单循环 - 排斥模型提供了一种统一的机制，可以解释如何真核SMC粘着蛋白复合物形成拓扑结构域（TADS）中的真核生物如何 SMC冷凝蛋白配合物将紧凑的DNA紧凑成棒状姐妹染色单体，以及细菌SMC冷凝蛋白解决新复制的起源。但是，该模型提出了一个重要的问题：SMC复合物如何当染色体被大量蛋白涂有并通过复制作用时，挤出DNA回路转录机？以及如何从染色体中释放出拓扑加载的复合物？这项拟议的研究的目的是了解在细胞的背景下凝结蛋白作用的机制活动利用了我们开发的许多分子和细胞学工具。首先，我们会的确定冷凝剂在遇到复制体或其他冷凝素分子时的作用。第二，我们将表征冷凝素到达末端区域时如何从染色体中释放出来的。最后，我们将探索凝聚蛋白在多部分细菌基因组的组织和动态中的作用，既包含圆形染色体和线性染色体。综上所述，拟议的工作有可能提供所有生物体中染色体折叠和压实的一般原理。