Initiation of DNA replication in Bacillus subtilis

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Reorganising the architecture of the bacterial genetic material is a complicated and dynamic process with crucial consequences to bacterial physiology. Significant reorganisation of the genetic material is required to set the scene for the start of DNA replication and also to assist the separation of the new genetic material from the old one. The molecular mechanisms behind DNA reorganisation and remodelling are not understood. We have recently discovered that two essential replication proteins known as DnaD and DnaB from the bacterium Bacillus subtilis exhibit significant opposing DNA-remodelling activities. In an effort to establish whether these remodelling activities are of direct relevance to DNA replication and to bacterial physiology we are now concentrating our efforts to reveal the molecular mechanisms that underpin these remodelling activities and also to study the effects of limiting these two proteins in the cell. We are aiming to solve the crystal structures of the two domains of DnaD and also of the full-length protein. Mutagenesis methods in parallel with the structural studies but also assisted by the forth-coming structures, together with supercoiling and genetic complementation experiments will be used to study the mechanisms of DNA remodelling and their significance to bacterial physiology. The findings of this study will be crucial if we are to undertand how the genetic material is reorganised in relation to DNA replication in a large class of bacteria known as gram positives. This class of bacteria contains important pathogens like Staphylococcus aureus (responsible for MRSA infections) and our findings will be of general applicability to the discovery of new antibiotic targets.