The Spatial and Temporal Integration of Chromosome Segregation and Cytokinesis

染色体分离和细胞分裂的时空整合

• 批准号: 8125755
• 负责人: Paola E Mera
• 金额: $ 4.84万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8125755
• 关键词: Bacteria; Bacterial Proteins; Biochemical; Caulobacter; Caulobacter crescentus; Cell Cycle; Cell Cycle Progression; Cell division; Cells; Chromosome Segregation; Chromosomes; Cleaved cell; Cytokinesis; DNA; Defect; Development; Drug Delivery Systems; Engineering; Eukaryota; Event; Generations; Genetic; Goals; Human; Image; Lead; Malignant Neoplasms; Mediating; Organism; Prokaryotic Cells; Proteins; Replication Initiation; Research; Resolution; Role; Scheme; Signal Transduction; Site; Structure; Study models; Variant; Work; antimicrobial drug; chromosome replication; daughter cell; imaging modality; mutant; novel; prevent; protein function; segregation

DESCRIPTION (provided by applicant): Progression through the cell cycle requires exquisite coordination between DNA replication initiation and the multiple events that must take place in a timely and spatially-specific manner. Proteins involved in replication initiation are remarkably similar in eukaryotes and prokaryotes. Decades of research revealed in fine detail how these proteins function to initiate replication. However, it is becoming increasingly apparent that these proteins also mediate non-replication functions. Little is known about how these functions are coordinated with chromosome replication. The goal of this proposal is to define the mechanisms that integrate multiple cell cycle functions in Caulobacter crescentus, specifically focusing on the bacterial protein responsible for replication initiation, DnaA. Caulobacter is an ideal model for studying bacterial cell cycle regulatory circuitry due to the simultaneous replication and polar segregation of its single chromosome and its asymmetric cell division. Recently, a dnaA mutant that disrupts the coordination of chromosome replication and spatial/temporal control of cytokinesis was identified. The specific aims of this proposal are to determine the role of DnaA in mediating (a) nucleoid occlusion at the incipient division site and (b) the coordination of chromosomal segregation with division site selection using high-resolution imaging combined with engineered strains with specific fluorescent tags and key cell division protein depletions. PUBLIC HEALTH RELEVANCE: Cell division entails exquisite coordination of multiple events involved in cell cycle progression. In human, erroneous coordination of these events can cause fatal developmental defects including cancer. A clear understanding of the mechanisms used by bacteria to accomplish such exquisite coordination can reveal common schemes used across evolutionary diverse organisms, including human.

描述（由申请人提供）：细胞周期的进展需要DNA复制起始和多个事件之间的精确协调，这些事件必须以及时和空间特异性的方式发生。真核生物和原核生物中参与复制起始的蛋白质非常相似。几十年的研究详细揭示了这些蛋白质如何启动复制的功能。然而，越来越明显的是，这些蛋白质也介导非复制功能。关于这些功能如何与染色体复制协调，我们知之甚少。本研究的目标是确定新月形茎状杆菌多种细胞周期功能整合的机制，特别是专注于负责复制起始的细菌蛋白dna。茎状杆菌由于其单染色体同时复制和极性分离以及细胞分裂不对称，是研究细菌细胞周期调控回路的理想模型。最近，发现了一个破坏染色体复制协调和细胞质分裂时空控制的dna突变体。该提案的具体目的是确定dna在介导(a)在分裂初期位点的类核阻断和(b)染色体分离与分裂位点选择的协调中的作用，使用高分辨率成像结合具有特定荧光标记和关键细胞分裂蛋白消耗的工程菌株。