Function of type1A topoisomerases in bacterial chromosome segregation

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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 most be faithfully accomplish before cell division, is the segregation of the replicated genetic material (chromosomes) to each end of the cell, so that each daughter cell can receive one chromosome following division. With a full set of the 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, chromosome segregation will not be possible. DNA topoisomerases, by cutting DNA and by allowing strand passage and religation solve the topological problem associated with the progression of replication complexes. Topoisomerases from the bacterium Escherichia coli have been well characterized in vitro in term of their catalytic properties and their ability to work during replication. However, little is known about their actual function in the cell and their regulation with the cell cycle. The main goal of our research project is to characterize the roles of the various DNA topoisomerases in chromosome replication and segregation in E. coli cells. Modern microscopic techniques allowing the visualization of chromosomes and proteins in living cells together with molecular biology, genetic and biochemical approaches will be used to characterize the roles of the various topoisomerases in the cell cycle. The ultimate goal of our research program is to understand how bacteria regulate the major events of their cell cycle to allow the faithful transmission of their genetic material to daughter cells.