Regulation of genome duplication requires exquisite control to ensure proper transmission of genetic material from mother cell to daughter cell and to prevent the genome aberrations that are associated with cancer cells. Importantly, the replication machinery must respond to changes in chromatin structure and cell cycle parameters that are associated with cellular differentiation to maintain genome integrity. Although this is a fundamental aspect of genome duplication, the underlying molecular mechanisms and critical factors responsible for responding to these changes remain poorly understood.
Drosophila provides an ideal model system to understand, mechanistically, how the DNA replication program responds to changes in cellular differentiation and development. We are using a combination of proteomic, genomic, cell biological, genetic and biochemical approaches to uncover and characterize fundamental aspects of genome duplication and stability.