Our goal is to understand the 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.
To ensure proper chromosome segregation, spindle microtubules must be attached to kinetochores, multi-protein complexes that are assembled on the centromere, a specialized DNA sequence on a chromosome. In addition, the centromere is the site where cohesion is established to link two sister chromatids together, which is essential for proper chromosome segregation. Thus, the centromere is the hub for orchestration of chromosome segregation. Using human cell culture, we are currently studying the following mechanisms that govern chromosome segregation: 1) How is centromeric cohesion protected and de-protected during mitosis? 2) How are stable kinetochore-microtubule interactions achieved during mitosis? 3) What are the functions of centromeric transcription and how is it regulated?
Understanding how chromosome instability contributes to aging and aging-related diseases.
Zhang Q, Hu L, Chen Y, Tian W*, and Liu H* (2020) Multisite Phosphorylation Determines the Formation of Ska-Ndc80 Macro-complexes That Are Essential for Chromosome Segregation during Mitosis. Mol Biol Cell. 2020 Aug 1;31(17):1892-190.
Zhang Q, Liu H* (2020) Functioning mechanisms of Shugoshin-1 in centromeric cohesion during mitosis. Essays Biochem. 2020 May 26;. doi: 10.1042/EBC20190077. (Invited review)
Qu Q, Zhang Q, Yang L, Chen Y, Liu H* (2019) SET binding to Sgo1 inhibits Sgo1-cohesin interactions and promotes chromosome segregation. J Cell Biol. 2019 Aug 5;218(8):2514-2528.
Hu L, Huang H, Hei M, Yang Y, Li S, Liu Y, Dou Z, Wu M, Li J, Wang GZ, Yao X, Liu H, He X, Tian W (2019) Structural analysis of fungal CENP-H/I/K homologs reveals a conserved assembly mechanism underlying proper chromosome alignment. Nucleic Acids Res. 2019 Jan 10;47(1):468-479.
Palozola KC, Liu H, Nicetto D, Zaret KS (2018) Low-Level, Global Transcription during Mitosis and Dynamic Gene Reactivation during Mitotic Exit. Cold Spring Harb Symp Quant Biol. 2018 Jan 18. pii: 034280.
Zhang Q, Chen Y, Yang L, Liu H* (2018) Multitasking Ska in Chromosome Segregation: Its Distinct Pools Might Specify Various Functions. Bioessays, 2018 Jan 23. doi: 10.1002/bies.201700176. (Invited review)
Palozola KC, Donahue G, Liu H, Grant GR, Becker JS, Cote A, Yu H, Raj A, Zaret KS. (2017) . Mitotic transcription and waves of gene reactivation during mitotic exit. Science, 2017 Oct 6;358(6359):119-122.
Zhang Q, Sivakumar S, Chen Y, Gao H, Yang L, Yuan Z, Yu H, and Liu H* (2017) Ska3 Phosphorylated by Cdk1 Binds Ndc80 and Recruits Ska to Kinetochores to Promote Mitotic Progression. Curr Biol 27(10):1477-1484.
Liu H* (2016) Insights into Centromeric Transcription in Mitosis. Transcription. 2016;7(1):21-5. (Invited review)
Liu, H* (2016) Linking lncRNA to genomic stability. Sci China Life Sci. 2016 Mar;59(3):328-9. (Invited review)
Before 2016 (Selected):
Liu, H, Qu, Q., Warrington R., Rice, A., Cheng N., and Yu, H., (2015) Mitotic Transcription Installs Sgo1 at centromeres to Coordinate Chromosome Segregation. Molecular Cell, 59(3), 426-436.
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, 21, 864-870.
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.)
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.
The full list of publication can be found at: https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/The citations can be found at: https://scholar.google.com/citations?user=0q2RV00AAAAJ&hl=en