Chromosome Dynamics in Bacillus Subtills

枯草芽孢杆菌的染色体动力学

基本信息

批准号：
10153802
负责人：
DAVID Z RUDNER
金额：
$ 37.29万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10153802
关键词：
ATP Hydrolysis ATP phosphohydrolase Bacillus Bacillus subtilis Bacteria Bacterial Chromosomes Binding Sites Biochemistry Biological Assay Biological Models Biological Process Cell Cycle Cells ChIP-seq Chromatin Loop Chromosome Arm Chromosome Segregation Chromosome Structures Chromosomes Colon Carcinoma Complex Cytology DNA Data Development Distal Ensure Eukaryota Genetic Transcription Hi-C Human In Vitro Interphase Left Maintenance Malignant Neoplasms Mediating Mitosis Modeling Molecular Morphology Movement Mutation Neurofibrillary Tangles Organism Pattern Play Process Proteins Replication Origin Resolution Role Sister Sister Chromatid Site Staphylococcus aureus Structure System T-Cell Lymphoma Testing Travel arm chromosome conformation capture cohesin condensin dimer experimental study in vitro activity in vivo insight mutant prevent recombinase segregation therapeutic target time use virtual

项目摘要

Compaction and resolution of replicated chromosomes into morphologically and spatially distinct sister chromatids is essential for faithful DNA segregation in all organisms, but the molecular mechanisms that underlie these processes are poorly understood. In bacteria, chromosome segregation is largely driven by DNA compaction, which is thought to occur by the orderly folding of chromosomes along adjacent DNA segments drawing replicated sisters in on themselves and away from each other. In virtually all organisms, Structural Maintenance of Chromosomes (SMC) condensin complexes play a central role in this process but how these ring-shaped ATPase function has remained unclear. In Bacillus subtilis, condensin rings are topologically loaded onto the chromosome adjacent to the origin of replication by the partitioning protein ParB bound to centromeric parS sites. Using chromosome conformation capture (Hi-C) and ChIP-seq, we discovered that these complexes then travel down the left and right chromosome arms all the way to the terminus while tethering the two arms together. Our findings support a generalizable model in which SMC complexes act along adjacent DNA segments by processively enlarging DNA loops. In this model, these ring-shaped complexes encircle the DNA flanking their loading site, tethering the duplexes together. As these tethers move away from their loading sites they generate loops. Loop- formation ensures that these complexes act along adjacent DNA segments and therefore resolve rather than tangle sister chromosomes. In B. subtilis, processive loop enlargement centered on origin-proximal parS sites draws sister origins in on themselves and away from each other. De novo loop formation along chromosome arms in eukaryotes can also explain how condensin complexes compact and resolve sister chromatids during mitosis and provides a mechanism for the formation of transcriptionally insulated domains (also called topologically associated domains or TADs) by SMC cohesin complexes during interphase. Our studies on the B. subtilis SMC complex highlights the importance of using simple model systems to study conserved cell biological processes. The experiments described in this proposal build on our recent discoveries and preliminary findings to define how these broadly conserved complexes generate DNA loops; how these ring- shaped tethers are removed when they reach the replication terminus; and the role of condensin in remodeling the bacterial chromosome during the replication-segregation cycle.

在形态和空间上，重复的染色体的压实和分辨率染色单体对于所有生物体中忠实的DNA分离至关重要，但是分子机制这些过程的理解很少。在细菌中，染色体隔离在很大程度上是由 DNA压实，被认为是通过沿相邻DNA的染色体有序折叠而发生的片段在自己和彼此之间绘制复制的姐妹。在几乎所有生物中，染色体的结构维护（SMC）凝结蛋白复合物在此过程中起着核心作用，但这些环形ATPase功能如何保持不清楚。在枯草芽孢杆菌中，在拓扑上，将冷凝蛋白环加载到与起源相邻的染色体上通过分配蛋白质PAR的复制与中心层面位点结合。使用染色体构象捕获（HI-C）和芯片隔离，我们发现这些复合物然后向左和向右传播染色体手臂一直到终点站，同时将两个手臂绑在一起。我们的发现支持可概括的模型，其中SMC复合物通过过程扩大而沿相邻DNA片段作用 DNA环。在此模型中，这些环形复合物环绕着其载荷位点的DNA，束缚双工一起。当这些系tethers远离其产生循环的加载位点时。环形- 形成确保这些复合物沿相邻的DNA片段作用，因此可以解决而不是纠缠姐妹染色体。在枯草芽孢杆菌中，以原点为中心的过程循环扩大位点为中心吸引姐妹起源于自己，彼此远离。沿着染色体的从头循环形成真核生物中的武器还可以解释如何在有丝分裂并提供了形成转录绝缘域的机制（也称为 SMC粘蛋白复合物在相间期间与拓扑相关的结构域或TAD）。我们关于 B.枯草厂SMC复合物突出了使用简单模型系统研究保守细胞的重要性生物过程。本提案中描述的实验建立在我们最近的发现和初步发现，以定义这些宽阔保守的复合物如何产生DNA环；这些环如何当形状的系数到达复制末端时，它们被去除；以及冷凝蛋白在在复制 - 分离周期中重塑细菌染色体。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Condensin promotes the juxtaposition of DNA flanking its loading site in Bacillus subtilis.

DOI：
10.1101/gad.265876.115
发表时间：
2015-08-01
期刊：
Genes & development
影响因子：
10.5
作者：
Wang X;Le TB;Lajoie BR;Dekker J;Laub MT;Rudner DZ
通讯作者：
Rudner DZ

Respiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in Bacillus subtilis and Escherichia coli.

DOI：
10.1038/s41598-020-79811-z
发表时间：
2021-01-08
期刊：
Scientific reports
影响因子：
4.6
作者：
Yang CK;Kashyap DR;Kowalczyk DA;Rudner DZ;Wang X;Gupta D;Dziarski R
通讯作者：
Dziarski R

A dynamic, ring-forming MucB / RseB-like protein influences spore shape in Bacillus subtilis.

DOI：
10.1371/journal.pgen.1009246
发表时间：
2020-12
期刊：
PLoS genetics
影响因子：
4.5
作者：
Luhur J;Chan H;Kachappilly B;Mohamed A;Morlot C;Awad M;Lyras D;Taib N;Gribaldo S;Rudner DZ;Rodrigues CDA
通讯作者：
Rodrigues CDA

Peptidoglycan hydrolysis is required for assembly and activity of the transenvelope secretion complex during sporulation in Bacillus subtilis.

DOI：
10.1111/mmi.12322
发表时间：
2013-09
期刊：
Molecular microbiology
影响因子：
3.6
作者：
Rodrigues CD;Marquis KA;Meisner J;Rudner DZ
通讯作者：
Rudner DZ

CtpB assembles a gated protease tunnel regulating cell-cell signaling during spore formation in Bacillus subtilis.

DOI：
10.1016/j.cell.2013.09.050
发表时间：
2013-10-24
期刊：
Cell
影响因子：
64.5
作者：
Mastny M;Heuck A;Kurzbauer R;Heiduk A;Boisguerin P;Volkmer R;Ehrmann M;Rodrigues CD;Rudner DZ;Clausen T
通讯作者：
Clausen T