molecular mechanisms of chromosome segregation.
Aneuploidy is one of the hallmarks in cancer cells. It is known to promote the development of cancer. A major cause of aneuploidy is derived from chromosome missegregation in mitosis. Therefore, a better understanding of the mechanisms of proper chromosome segregation will help decipher the underlying causes of cancer and provide theoretical bases for clinical applications.
Our long-term goal is to understand the molecular mechanisms that govern precise chromosome segregation. Several aspects play essential roles in chromosome segregation: spindle poles, kinetochore-microtubule interaction, spindle checkpoint and cohesion. My current research focuses on the regulation of cohesin-mediated cohesion.
The cohesin complex plays an essential role in chromosome segregation. It is loaded onto chromosomes in G1/telophase, and removed from chromosomes in mitosis. The conserved cohesin protector, Shugoshin, is critical for the proper regulation of cohesin and chromosome segregation. Dysregulation of human Sgo1 leads to chromosome missegregation that contributes to aneuploidy. Using a combination of genetic, cell biological and biochemical approaches, we uncovered the molecular mechanisms in which Sgo1 protects centromeric cohesin in early mitosis. Our recent work also revealed the mechanism that loads Sgo1 at centromeres, which is essential for the proper functions of Sgo1. Surprisingly, we found that RNA polymerase II (Pol II)-dependent transcription plays essential roles in installing Sgo1 at centromeres in mitosis, and that the mitotic kinase Bub1 regulates active RNA Pol II transcription. Currently, we are trying to understand the regulation of centromeric transcription and its roles in centromeric cohesion and chromosome stability.
Understanding how chromosome instability contributes to aging and aging-related diseases.
1. Hong Liu, Qianhui Qu, Ross Warrington, Allyson Rice, Ningyan Cheng, and Hongtao Yu. (2015) Mitotic Transcription Installs Sgo1 at centromeres to Coordinate Chromosome Segregation. (Molecular Cell, http://dx.doi.org/10.1016/j.molcel.2015.06.018)
2. Hara, K., Zheng, G., Qu, Q., Liu, H., Ouyang, Z., Chen, Z., Tomchick, D.R., Yu, H. (2014) Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion. Nat Struct Mol Biol 2014 Aug 31. doi: 10.1038/nsmb.2880.
3. McKnight K., Liu H., Wang, Y. (2014). Replicative stress induces intragenic transcription of the ASE1 gene that negatively regulates Ase1 activity. Curr Biol 24, 1101-1106.
4. Liu, H., Jia, L., and Yu, H. (2013). Phospho-H2A and cohesin specify distinct tension-regulated Sgo1 pools at kinetochores and inner centromeres. Curr Biol 23, 1927-1933.
(Comment in: Chromosome segregation: Learning to let go. Curr Biol. 2013 Oct 7;23(19):R883-5.)
5. Liu, H., Rankin, S., and Yu, H. (2013). Phosphorylation-enabled binding of SGO1-PP2A to cohesin protects sororin and centromeric cohesion during mitosis. Nat Cell Biol 15, 40-49.
6. Jin, F.*, Liu, H.*, Li, P., Yu, H.G., and Wang, Y. (2012). Loss of function of the Cik1/Kar3 motor complex results in chromosomes with syntelic attachment that are sensed by the tension checkpoint. PLoS Genet 8, e1002492. (* Co-first author)
7. Liu, H.*, Jin, F*., Liang, F., Tian, X., and Wang, Y. (2011). The Cik1/Kar3 motor complex is required for the proper kinetochore-microtubule interaction after stressful DNA replication. Genetics 187, 397-407. (* Co-first author)
8. Liu, H. and Yu, H. (2010). Mad revival of cancer. Cell Res 20, 394-396. (Review)
9. Liang, F., Jin, F., Liu, H., and Wang, Y. (2009). The molecular function of the yeast polo-like kinase Cdc5 in Cdc14 release during early anaphase. Mol Biol Cell 20, 3671-3679.
10. Jin, F., Liu, H., Liang, F., Rizkallah, R., Hurt, M.M., and Wang, Y. (2008). Temporal control of the dephosphorylation of Cdk substrates by mitotic exit pathways in budding yeast. Proc Natl Acad Sci USA 105, 16177-16182.
11. Liu, H., Liang, F., Jin, F., and Wang, Y. (2008). The coordination of centromere replication, spindle formation, and kinetochore-microtubule interaction in budding yeast. PLoS Genet 4, e1000262.
12. Liu, H. and Wang, Y. (2006). The function and regulation of budding yeast Swe1 in response to interrupted DNA synthesis. Mol Biol Cell 17, 2746-275.