Bacterial type 1A topoisomerases in genome stability.

细菌细胞生命的关键步骤是分裂产生两个相同的子细胞。这一事件使其代代相传。然而，在细胞分裂之前必须忠实完成的一个关键事件是将复制的遗传物质（染色体）分离到细胞的每一端，同时保持基因组的稳定性，以便每个子细胞可以在分裂后接受一条染色体。有了母细胞的全套基因，每个子细胞都能够生长和分裂。由于DNA的双螺旋性质，DNA链的缠结在复制过程中不可避免地发生。如果不适当和迅速地去除，这些缠绕将最终阻止复制复合物的进展，因此，将发生DNA损伤，染色体分离将是不可能的。DNA拓扑异构酶通过切割DNA并通过允许链通过和重新连接来解决与复制复合物的进展相关的拓扑问题。IA型拓扑异构酶在真核细胞中的染色体分离和基因组稳定性中起重要作用。我们最近的研究结果表明，1A型酶从模式生物大肠杆菌，发挥类似的作用，染色体分离和基因组的稳定性。然而，人们对IA型酶如何执行其任务知之甚少。我们未来五年研究的主要目标是描述E。大肠杆菌IA型拓扑异构酶作用于基因组以维持其稳定性。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。我们研究计划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。

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.