How bacterial SMC complexes organize chromosomes

细菌 SMC 复合体如何组织染色体

• 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
• 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

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 在生命的所有领域中，染色体的维持（SMC）复合体在这些过程中起着中心作用。 这些环状ATP酶具有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，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复合物利用ATP水解挤出DNA环。在 例B。在枯草杆菌中，SMC凝聚素复合物装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转移，将它们连接在一起。通过这种方式， 产生一个以原点为中心的染色体环，将姐妹染色体吸引到自己身上， 彼此远离。这个优雅简单的循环挤出模型提供了一个统一的机制来解释如何 真核细胞SMC粘附素复合物在间期形成拓扑相关结构域（TADs），真核细胞如何 SMC凝聚素将紧密DNA复合成杆状姐妹染色单体以及细菌SMC凝聚素 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复合物如何 当染色体被许多蛋白质包被并受到复制作用时， 转录机器拓扑负载的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凝聚素在细胞内的作用机制。 活动，利用我们开发的许多分子和细胞学工具。一是 确定凝聚素在遇到复制体或其他凝聚素分子时如何发挥作用。二是 将表征当它们到达末端区域时，凝聚素如何从染色体释放。 最后，我们将探讨凝聚素在多组分细菌基因组的组织和动力学中的作用， 含有环状和线状染色体。总之，拟议的工作有可能提供 所有生物体染色体折叠和压缩的一般原理。