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: 8307562
• 负责人: Paola E Mera
• 金额: $ 5.22万
• 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/8307562
• 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.

描述（由申请人提供）：通过细胞周期的进展需要DNA复制启动与必须及时和空间特定方式进行的多个事件之间的精致协调。在真核生物和原核生物中，参与复制起始的蛋白质非常相似。数十年的研究详细揭示了这些蛋白质如何发挥复制。但是，越来越明显的是，这些蛋白质还介导了非复制功能。对于这些功能如何与染色体复制协调的知识知之甚少。该提案的目的是定义整合花椰菜齿状菌中多个细胞周期功能的机制，特别是针对负责复制起始的细菌蛋白DNAA。 Caulobacter是研究细菌细胞周期调节电路的理想模型，这是由于其单个染色体及其不对称细胞分裂的同时复制和极性分离。最近，确定了破坏染色体复制和空间/时间控制细胞因子的配位的DNAA突变体。该提案的具体目的是确定DNAA在初期分裂位点的介导（a）核苷闭塞中的作用，（b）使用高分辨率成像结合了与工程菌株与特定荧光标签和钥匙细胞分裂蛋白质消耗相结合的高分辨率成像与分裂位点选择的协调。