How bacterial SMC complexes organize chromosomes

细菌 SMC 复合体如何组织染色体

• 批准号: 10182533
• 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
• 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/10182533
• 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

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 复制染色体的组织和分离是生命系统的基础。结构性 染色体的维持(SMC)复合体在生命的所有领域中都在这些过程中发挥着核心作用。 这些环状ATPase共享共同的结构和亚基间的接触，与共同的 作用机制。在过去的五年里，对枯草芽孢杆菌和真核生物的研究提供了 令人信服的体内和体外证据表明，SMC复合体利用ATP水解来挤出DNA环。在 在枯草杆菌的情况下，SMC凝集素复合体被装载在复制起点附近的着丝粒部分位点， 然后将左右染色体臂向下移位，将它们捆绑在一起。通过这种方式，凝集素 生成以吸引姐妹染色体自身的原点为中心的单个染色体环，并 彼此远离。这个非常简单的环路挤出模型提供了一个统一的机制来解释 真核细胞中的SMC粘附素复合体在间期形成拓扑结合结构域(TADS)，如何真核 SMC凝集素复合体将DNA压缩成杆状姐妹染色单体，以及细菌SMC凝集素是如何 解析新复制的原点。然而，这个模型提出了一个重要的问题：SMC复合体是如何 当染色体被大量蛋白质覆盖并通过复制和作用于染色体时，挤出DNA环 转录机器？而具有拓扑结构的复合体是如何从染色体中释放出来的？ 这项拟议的研究的目的是在细胞的背景下了解凝集素的作用机制。 活动，利用我们开发的许多分子和细胞学工具。首先，我们将 确定凝聚素在遇到复制体或其他凝集素分子时的作用。第二，我们 将描述当凝集素到达染色体末端区域时如何从染色体中释放凝聚素。 最后，我们将探索凝聚素在多部分细菌基因组的组织和动态中的作用 既含有圆形染色体又含有线形染色体。综上所述，拟议的工作有可能提供 染色体在所有生物体中折叠和紧凑的一般原理。