Cytological studies in several bacterial species have shown that multiple proteins involved in DNA replication, repair and chromosome condensation are highly enriched at the cell center. Increasing the localized concentration of such proteins is thought to facilitate the processivity and efficiency of DNA replication. Multiple lines of evidence, from phage infected bacterial cells to mammalian cells, indicate that there is a multi-enzyme complex involved in the synthesis of deoxynucleoside triphosphates (dNTPs), physically associated with components of the DNA replication machinery. Although the coupling of these complexes is non-essential, the implication for coupling is that there would be an increased concentration of dNTPs at active sites of replication, maximizing the efficiency and stability of replication forks. This research is aimed at understanding the processes that must be spatially and temporally controlled to maximize the efficiency of DNA replication: (i) by addressing the coordination of nucleotide synthesis and DNA replication and (ii) by identifying factors that constitute or are associated with the replisome, a multi-enzyme complex or 'factory' responsible for DNA replication. A key feature of these studies is that they have the potential to define the protein interaction network associated with DNA replication. Understanding these processes is of fundamental importance to all cells because faithful and accurate transmission of genetic information from mother cell to daughter cell is crucial in all organisms. Additionally, loss of replication fork stability can lead to fork collapse, resulting in mutation or loss of viability. Graduate and undergraduate students are critical participants in this research project.
