Bik Tye is visiting Professor at the HKUST and Professor Emeritus at Cornell University. She received her education and training from Wellesley College (BA, 1969), University of California, San Francisco (M.Sc. 1971), MIT (PhD, 1974) and Stanford University (Postdoc, 1977). Her interest in DNA replication began with her postdoctoral training at Stanford where she discovered that short Okazaki fragments were generated by aberrant DNA repair in E. coli. At Cornell, her first project was to screen for yeast DNA replication initiation mutants called mcm that exhibited an ARS-specific minichromosome maintenance defect. The MCM2-7 complex was later shown to form the catalytic core of the replicative helicase. Together with Dr. Yuanliang Zhai, they established the DNA Replication Group at HKUST to study the high-resolution structures of MCM-associated replication complexes in yeast.

Research Question

Every time a cell divides, the entire genome of 6 billion base pairs (in the case of human) has to be replicated with the utmost accuracy and efficiency. This elaborate process of DNA replication is regulated at every step of the way from origin licensing at G1 phase, to initiation at the G1/S phase transition, to elongation synthesis during S phase, to termination at the end of S phase and the separation of the sister chromatids at G2-M phase. Our group is interested in understanding the molecular mechanism of each of these steps using high resolution cryo-EM structures of the DNA replication machinery as the framework to interpret biochemical and genetic data for model building.

Research Approach

We use the budding yeast as our model system because of its amenable genetics that allows the purification of large quantities of stage-assembled replication complexes endogenously for structural analyses. In collaboration with Professor Ning Gao’s group at Peking University, we use cryo-EM to obtain high-resolution structures of mega complexes of the macromolecular replication machines. In collaboration with Professor Guang Zhu, we use NMR spectroscopy to study interactions of localized flexible regions within the molecular machines. In collaboration with Professor Xuhui Huang, we use computational simulations to study the dynamics of these molecular machines in motion.

Representative Publications

1. Li N, Lam WH, Zhai Y, Cheng J, Cheng E, Zhao Y, Gao N, Tye BK Structure of the origin recognition complex bound to DNA replication origin, Nature (2018). 559:217-222. DOI: 10.1038/s41586-018-0293-x
2. Zhai YL, Chen E, Wu H, Li N, Yung P, Gao N, Tye BK Open-ringed structure of the Cdt1–Mcm2–7 complex as a precursor of the MCM double hexamer, Nature Structural & Molecular Biology (2017) 24:300-308. DOI: 10.1038/nsmb.3374
3. Zhai YL, Li N, Jiang H, Huang X, Gao N and Tye BK. Unique roles played by each of the non-identical MCM subunits in DNA Replication Licensing. Molecular Cell (2017) 67:168-179 DOI: 10.1016/j.molcel.2017.06.016. Review.
4. Li N, Zhai YL, Zhang Y, Li W, Yang M, Lei J, Tye BK, Gao N. Structure of the eukaryotic MCM complex at 3.8 Å, Nature (2015) 524:168-191. DOI: 10.1038/nature14685 Bochman M, Schwacha A Strand separation unravelled, Nature (2015). DOI: 10.1038/nature14643
5. Maine, G., Sinha, P. and Tye, B.K. (1984) Mutants of S. cerevisiae defective in the maintenance of minichromosomes. Genetics 106: 365–385.

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