Bacterial type 1A topoisomerases in genome stability.

细菌细胞生命中的关键一步是分裂，产生两个完全相同的子细胞。这一事件使其代代相传。然而，在细胞分裂之前必须忠实地完成的一件关键事情是，在保持基因组稳定的同时，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都能获得一条染色体。有了母细胞的全套基因，每个子细胞将能够生长和分裂。由于DNA的双螺旋性质，在复制过程中不可避免地会发生DNA链的纠缠。如果不能正确和迅速地去除，这些缠绕在一起的物质最终会阻碍复制复合体的发展，因此，DNA损伤将会发生，染色体将不可能分离。DNA拓扑异构酶，通过切割DNA，允许链通过和重新连接，解决了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性中起着重要作用。我们最近的结果表明，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性方面发挥着类似的作用。然而，关于IA型酶是如何完成其任务的知之甚少。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，以允许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.