Bacterial type 1A topoisomerases in genome stability.

细菌 1A 型拓扑异构酶的基因组稳定性。

• 批准号: RGPIN-2016-04205
• 负责人: Drolet, Marc
• 金额: $ 2.26万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614913
• 关键词: Bacterial; type; 1A; topoisomerases; genome

A key step in the life of a bacterial cell is its division to generate two identical daughter cells. This event allows its perpetuation from generation to generation. However, one key event that must be faithfully accomplish before cell division, is the segregation of the replicated genetic material (chromosomes) to each end of the cell while maintaining the stability of the genome, so that each daughter cell can receive one chromosome following division. With a full set of genes from the mother cell, each daughter cell will be able to grow and divide. Because of the double-helical nature of the DNA, entanglement of the DNA strands inevitably occurs during replication. If not properly and rapidly removed, these intertwines will eventually block the progression of the replication complex and, as a consequence, DNA damages will occur and chromosome segregation will not be possible. DNA topoisomerases, by cutting DNA and by allowing strand passage and re-ligation solve the topological problem associated with the progression of replication complexes. Type IA topoisomerases have been shown to play major roles in chromosome segregation and genome stability in eukaryotic cells. Our recent results indicate that type 1A enzymes from the model organism Escherichia coli, play similar roles in chromosome segregation and genome stability. However, little is known about how type IA enzymes perform their tasks. The main goal of our research over the next five years is to characterize the precise mechanisms by which E. coli type IA topoisomerases act on the genome to maintain its stability. To achieve our objective, we will use state-of-the-art single-cell and whole-genome approaches. The ultimate goal of our research program is to understand how cells regulate the major events of their cell cycle to allow the faithful transmission of their genetic material to daughter cells.

细菌细胞生命的关键一步是分裂产生两个相同的子细胞。这一事件使其得以代代相传。然而，在细胞分裂之前必须忠实完成的一个关键事件是，在保持基因组稳定性的同时，将复制的遗传物质（染色体）分离到细胞的两端，以便每个子细胞在分裂后可以获得一条染色体。有了母细胞的全套基因，每个子细胞就能生长和分裂。由于DNA的双螺旋性质，在复制过程中不可避免地会发生DNA链缠结。如果不能正确和迅速地去除，这些缠结最终会阻碍复制复合体的进展，结果，DNA损伤将发生，染色体分离将不可能。DNA拓扑异构酶通过切割DNA并允许链通过和重新连接来解决与复制复合体进展相关的拓扑问题。在真核细胞中，IA型拓扑异构酶在染色体分离和基因组稳定中起着重要作用。我们最近的研究结果表明，来自模式生物大肠杆菌的1A型酶在染色体分离和基因组稳定中起着类似的作用。然而，对于IA型酶如何执行它们的任务，我们知之甚少。我们未来五年研究的主要目标是描述大肠杆菌IA型拓扑异构酶作用于基因组以维持其稳定性的精确机制。为了实现我们的目标，我们将使用最先进的单细胞和全基因组方法。我们研究项目的最终目标是了解细胞如何调节其细胞周期的主要事件，以便将其遗传物质忠实地传递给子细胞。