Bacterial type 1A topoisomerases in genome stability.

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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.