The long term goal of this research program is to understand how eukaryotic DNA replication is regulated during the cell cycle. This question is central to understanding the mechanisms that control cellular proliferation in normal cells, as well as the perturbations of normal growth control that result in cancer. We have chosen Schizosaccharomyces pombe as an experimental system because it has many similarities to higher eukaryotic cells and because it has already proved to be a powerful tool for probing cell cycle control. Our approach to problem of how DNA replication is regulated in S. pombe is twofold. First, we plan to use genetic and biochemical methods to identify and characterize genes that couple the basic cell cycle engine to the initiation of DNA replication. Second we will analyze the structure and function of the S pombe origin of replication, ARS1, with the aim of identifying and characterizing interacting proteins involved in initiation. We expect that information obtained in our studies will complement that obtained from the study of S. cerevisae and will be directly relevant to the control of DNA replication in higher eukaryotes.
| Callegari, A John; Kelly, Thomas J (2016) Coordination of DNA damage tolerance mechanisms with cell cycle progression in fission yeast. Cell Cycle 15:261-73 |
| Callegari, A John; Clark, Emily; Pneuman, Amanda et al. (2010) Postreplication gaps at UV lesions are signals for checkpoint activation. Proc Natl Acad Sci U S A 107:8219-24 |
| Houchens, Christopher R; Lu, Wenyan; Chuang, Ray-Yuan et al. (2008) Multiple mechanisms contribute to Schizosaccharomyces pombe origin recognition complex-DNA interactions. J Biol Chem 283:30216-24 |
| Dai, Jianli; Chuang, Ray-Yuan; Kelly, Thomas J (2005) DNA replication origins in the Schizosaccharomyces pombe genome. Proc Natl Acad Sci U S A 102:337-42 |
| Brown, G W; Kelly, T J (1999) Cell cycle regulation of Dfp1, an activator of the Hsk1 protein kinase. Proc Natl Acad Sci U S A 96:8443-8 |
| Brown, G W; Kelly, T J (1998) Purification of Hsk1, a minichromosome maintenance protein kinase from fission yeast. J Biol Chem 273:22083-90 |
