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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.

项目总结