Assembly and Dynamics of the DNA Replication Machine

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Cells in our body carry the same genetic information as that of the embryo we once were. Coded in DNA, the information is reliably transferred from mother to daughter cells thousands of times as we grow. Molecular machines work inside the cells to copy and maintain this genetic information. The study of these machines, and others working in different cellular processes, has been hindered by a major limitation of biochemistry: the impossibility of reconstructing intracellular conditions in test tubes.Outlined in this proposal is an alternative strategy to study DNA replication, one that involves moving away from attempts to reconstruct intracellular condition in vitro and instead obtaining relevant biochemical information directly from living cells. The long-term objective of this laboratory is to extract detailed mechanistic insights on the processes of DNA metabolism directly from living cells by capitalizing on recent advances in the field of microscopy. While in the current proposal the candidate will investigate two specific aspects of the DNA replication machine: its assembly early during the cell cycle and the mechanisms that prevent its premature disassembly prior to the completion of DNA replication.This work will help furthering a novel approach for the study of molecular events happening within cells. Use of this approach to study the assembly and stability of the replication machinery will provide unprecedented insight towards their understanding. Increased comprehension on the DNA replication machine in bacteria will help understanding how similar machines copy and maintain the chromosome in all other organisms.