Scholar Profile

Daniel J. Lew

Professor
Department of Pharmacology and Cancer Biology
Duke University
Box 3686
Durham, NC 27710
Voice: 919-613-8627
Fax: 919-681-1005
Email: daniel.lew@duke.edu
Personal Homepage
1995 Searle Scholar

Research Interests

The Morphogenesis Checkpoint in Saccharomyces cerevisiae

In the budding yeast S. cerevisiae, cell cycle progression is controlled by the Cdc28 protein kinase and cyclins. In particular, mitosis is triggered by activation of Cdc28 by Clb cyclins. In cells that cannot polarize the actin cytoskeleton or form a bud, mitosis is delayed due to a checkpoint control pathway that inhibits Cdc28. This checkpoint requires the SWE1 gene, encoding a kinase capable of phosphorylating Cdc28 on tyrosine 19, thus inhibiting its kinase activity. During the checkpoint-induced G2 delay, CLB transcription is repressed, while SWE1 transcription is induced: both of these contribute to lowering Cdc28 activity. However, we have found that both of these transcriptional responses are due to feedback loops rather than direct responses to the budding defect. Furthermore, cells that express moderate levels of CLBs or SWE1 from constitutive promoters retain the capacity to mount a checkpoint response, demonstrating that these transcriptional feedback loops are not essential for checkpoint function. Biochemical analysis of Swe1p is underway to determine whether Swe1p activity is directly regulated by the checkpoint.