Yanchang Wang, Ph.D. Assistant Professor of Cell Biology Department of Biomedical Sciences College of Medicine, Florida State University 1115 West Call Street Tallahassee, FL 32306-4300 Office: (850) 644-0402 Lab: (850) 645-2926 Dr. Wang's Faculty Profile
Research Interests
Yeast Cell Cycle Regulation The regulation of mitotic exit The key driving force of cell division is cyclin dependent kinase (CDK), a protein kinase conserved in all eukaryotic cells. Its activity is high during S and M phase as active CDK is required for DNA synthesis and chromosome segregation. After chromosome segregation, a signal transduction pathway, named mitotic exit network (MEN), inactivates CDK to favor the initiation of the next cell cycle. Cdc5 kinase is one of the components in MEN pathway. We found that Cdc5 promotes mitotic exit by directly phosphorylating Bfa1, a negative regulator of MEN. Bfa1 phosphorylation leads to its dissociation from Tem1, a GTPase that acts at the very top of MEN pathway. Therefore, Cdc5 promotes mitotic exit by inactivating Bfa1, the negative regulator of MEN. By screening genes that are toxic to cdc5-1 mutants, we have identified Amn1, a new protein that inactivates MEN pathway after cells exit mitosis. Amn1 binds to Tem1 protein and subsequently abolishes Tem1’s association with its downstream target Cdc15 kinase. In addition to Amn1, several components of phosphatase 2A (PP2A) have been identified to be toxic to cdc5-1 when overexpressed. We are currently investigating the negative roles of PP2A in mitotic exit. DNA damage response We are also interested in how eukaryotic cells sense and respond to stress in the form of damage to their genetic material. In response to DNA damage or DNA replication interference, cells arrest the cell cycle via cell cycle checkpoint pathways. Failure to do this can result in genomic instability and cancer in humans. The presence of DNA damage and the blockage of DNA replication activate a kinase cascade involving the Mec1, Rad53, and Chk1 protein kinases in yeast. Mec1 controls the activation of Rad53 and Chk1. Chk1 kinase phosphorylates the anaphase inhibitory protein Pds1 and prevents its degradation. We found that activated DNA damage checkpoint also inhibit mitotic exit by a yet identified mechanism. Another research interest in this laboratory is to find the link between DNA damage checkpoints and the cell cycle machinery by investigating how various cell cycle regulatory pathways respond to DNA damage in budding yeast. We will combine powerful cellular, genetic and biochemical approaches, along with the convenient yeast genomic database to uncover the regulatory networks and their components that govern cell cycle progression under normal and stressful environments.
Current Projects
The current research projects in mitotic exit regulation: 1. To understand the molecular mechanism of Amn1 protein degradation. 2. To explore mechanism that couples cytokinesis to mitotic exit pathway. 3. To investigate negative role of PP2A in mitotic exit. The current projects in DNA damage response: 1. To investigate how mitotic exit network response to DNA damage 2. To understand the molecular mechanism of DNA damage checkpoint recovery
Current Laboratory Members
Postdoctoral fellow: Graduate Student: Fengshan Liang Ph.D.: Chinese Academy of Sciences     Hong Liu M.S., B.S.: Sichuan University
Selected References
Wang Y*, Hu F*, Elledge SJ. (2000) The Bfa1/Bub2 GAP complex comprises a universal checkpoint required to prevent mitotic exit. Curr Biol. 2000 10(21):1379-82. (* equal contributor) Wang H, Liu D, Wang Y, Qin J, Elledge SJ. (2001) Pds1 phosphorylation in response to DNA damage is essential for its DNA damage checkpoint function. Genes Dev. 15(11):1361-72. Hu F*, Wang Y*, Liu D, Li Y, Qin J, Elledge SJ. (2001) Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Cell. 107(5):655-65. (* equal contributor) Li Y, Bachant J, Alcasabas AA, Wang Y, Qin J, Elledge SJ. (2002) The mitotic spindle is required for loading of the DASH complex onto the kinetochore. Genes Dev. 16(2):183-97. Wang Y, Shirogane T, Liu D, Harper JW, Elledge SJ. (2003) Exit from exit: resetting the cell cycle through Amn1 inhibition of G-protein signaling. Cell 112 (5):697-709 Wang Y. and Ng T. (2006) Phosphatase 2A negatively regulates mitotic exit in Saccharomyces cerevisiae. Mol. Biol Cell 17(1) 80-89 Liu H. and Wang Y. (2006) The Function and Regulation of Budding Yeast Swe1 in Response to Interrupted DNA Synthesis. Mol Biol Cell. 17:2746-56 (Epub Mar. 2006) Tang X. and Wang Y. (2006) Pds1/Esp1 dependent and independent sister chromatid separation in mutants defective for protein phosphatase 2A. Proc Natl Acad Sci U S A. 103:16290-16295 Jin F. and Wang Y. (2006) Budding yeast DNA damage adaptation mutants exhibit defects in mitotic exit. Cell Cycle 5:2914-9 Liang F. and Wang Y. (2007) DNA damage checkpoints inhibit mitotic exit by two different pathways. Mol. and Cell. Biol. 14:5067-5078 Li Y., Liang F., Jiang W., Yu F., Cao R., Ma Q., Dai X., Jiang J., Wang Y*., and Si S*. (2007) DH334, a Beta-carboline anti-cancer drug, inhibits the CDK activity of budding yeast. Cancer Biology and Therapy 6(8) [Epub ahead of print] * co-corresponding author Wang Y. (2007) Genome stability in yeast and its implications to the study of human cancer. Frontiers in Bioscience (in press)