What is life? Philosophers may have debates about the meaning of life, but biologists would answer that life is the ability of cells to grow and divide, passing on the hereditary information to the daughter cells. The cell cycle is the essence of this process. We focus on the transition from G1 to S phase and the initiation of DNA replication that is a major control checkpoint in the cell cycle. Normally, once a cell has replicated its DNA, it is committed to divide. Our studies are on characterization of origins of DNA replication where DNA synthesis begins.
- What features identify origins?
- How are origins regulated so that they are activated no more than once per S phase to perfectly duplicate the genome?
- How is this regulation overridden for site-specific re-replication, leading to DNA amplification that is a hallmark of many cancers?
- How does the cell recognize that it has grown to sufficient size to divide? Cell growth relies on ribosomes for protein synthesis, and we also study ribosomal RNA. Recently, we and others have found that inhibition of ribosome biogenesis blocks the entry to S phase, suggesting cross-talk with the initiation of DNA replication.