douzhen@@ustc.edu.cn (-@@- change to @)
Cell cycle and Mitosis
The embryonic development of and the maintenance of healthy adult of a eukaryotic organism depends on faithful mitosis. During mitosis, the duplicated genetic materials were transmitted into two daughter cells. Errors in mitosis will lead to aneuploidy daughter cells, and will promote tumorgenesis and other diseases. The morphology and structure of cells changed sharply during mitosis, although the time span of mitosis is short comparing to the whole cell cycle. The course of mitosis is highly dynamic and is under the fine regulation of mitotic kinases (e.g. CDK1, PLK1, Aurora A/B), protein phosphotase and Ubiquitin E3 ligase APC/C. The spindle assembly checkpoint (SAC) is a surveillance mechanism to safeguard the faithful chromosome segregation. Until all chromosomes achieved correct kinetochore-microtubule attachment, the cells enter anaphase due to the satisfaction of SAC. We are interested on the following scientific questions: 1. The molecular composition, assembly, structure and function of kinetochore; 2. The establishment of stable kinetochore-microtubule attachment; 3. Functions and regulations of mitotic kinases; 4. Functions and regulations of motor protein involved in mitosis; 5. The signaling pathway and molecular mechanism of SAC.
Education and research experience 1994.09-1998.07: Department of Biology,, Anhui University Major: Microbiology, Degree: Bachelor of Science 1998.09-2004.11: School of Life Sciences, USTC Major: Molecular and Cellular Biology, Degree: Ph.D. 2004.12-2007.04: School of Life Sciences, USTC Post-doctoral researcher 2005.05-2005.12: Morehouse School of Medicine, USA Visiting scholar 2007.05-2009.10: Max-Planck Institute of Biochemistry, Germany Post-doctoral researcher 2010.01-present: Hefei National Laboratary for Physical Science at the micro-scale, University of Science and Technology of China, Associated professor Research Interests Kinetochore and Mitosis; Mitotic kinases; Ubiquitin-proteasome system in cell cycle control; Genome instability and cancer. Honors Xia Jia-Hui scholarship for Symposium on Molecular Basis of Development and Disease (2002, Zhangjiajie, China) Scholarship to attend 5th Doctoral students conference of APRU (Association of Pacific Rim Universities) (2004, Sydney) Postdoctoral researcher fellowship from Max-Planck Society, Germany (2007-2009) Distinguished research paper award of School of Life Science, USTC (2015) Professional Membership Member of the American Society for Cell Biology Member of the Chinese Society of Cell Biology
Selected Publications (# equal contribution; * corresponding author )
- Dou Z, Liu X, Wang W, Zhu T, Wang X, Xu L, Abrieu A, Fu C, Hill DL, Yao X. 2015. Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment. Proc Natl Acad Sci U S A. 112(33): E4546-55.
- Wang X, Yu H, Xu L, Zhu T, Zheng F, Fu C, Wang Z, Dou Z. 2014. Dynamic autophosphorylation of Mps1 kinase is required for faithful mitotic progression. PLo ONE. 9 (9): e0104723.
- Zhu T#, Dou Z#, Qin B, Jin C, Wang X, Xu L, Wang Z, Zhu L, Liu F, Gao X, Ke Y, Wang Z, Aikhionbare F, Fu C, Ding X, Yao X. 2013. Phosphorylation of Microtubule-binding Protein Hec1 by Mitotic Kinase Aurora B Specifies Spindle Checkpoint Kinase Mps1 Signaling at the Kinetochore. J. Biol. Chem. 288: 36149-36159. (# equal contribution)
- Thebault P, Chirgadze DY, Dou Z, Blundell TL, Elowe S, Bolanos-Garcia VM. 2012. Structural and functional insights into the role of the N-terminal Mps1 TPR domain in the SAC (spindle assembly checkpoint). Biochem J. 448: 321-8.
- Dou Z, von Schubert C, K*rner R, Santamaria A, Elowe S and Nigg EA. 2011. Quantitative mass spectrometry analysis reveals similar substrate consensus motif for human Mps1 kinase and Plk1. PLoS ONE. 6(4):e18793.
- Hua S, Wang Z, Jiang K, Huang Y, Ward T, Zhao L, Dou Z*, Yao X*. 2011. CENP-U Cooperates with Hec1 to Orchestrate Kinetochore-Microtubule Attachment. J Biol Chem. 286: 1627-38. (* corresponding author)
- Zhao L, Chu J, Yuan K, Liu J, Yan F, Miao Y, Shaw A, Jin C, Dou Z*, Yao X*. 2010. Dimerization of CPAP orchestrates centrosome cohesion plasticity. J Biol. Chem. 285: 2488-97. (* corresponding author)
- Elowe S, Dulla K, Uldschmid A, Li X, Dou Z, Nigg EA. 2010. Uncoupling BubR1 spindle checkpoint and chromosome congression functions. J Cell Sci. 123: 84-94.
- Dou Z, Ding X, Zereshki A, Zhang Y, Zhang J, Wang F, Sun J, Huang H, Yao X. 2004. TTK kinase is essential for the centrosomal localization of TACC2. FEBS Lett. 572: 51-6.
- Dou Z, Sawagechi A, Zhang J, Luo H, Brako L, Yao, X. 2003. Dynamic distribution of TTK in HeLa cells: insights from an ultrastructural study. Cell Research 13: 443-449.