Prof. Yuanliang Zhai received his BSc (2001) and MPhil (2003) from Sun Yat-Sen University and his PhD (2010) in Biochemistry from the Hong Kong University of Science and Technology (HKUST). Following his graduation, he served as a postdoctoral fellow under the supervision of Prof. Bik Tye in the Division of Life Science at HKUST and later became a Research Assistant Professor in 2013. From 2015 to 2018, Prof. Zhai held the position of Junior Fellow at the Institute for Advanced Study of HKUST. Subsequently, he joined the School of Biological Sciences at the University of Hong Kong (HKU) as an Assistant Professor in 2018 and was promoted to Associate Professor in 2024. In 2025, he returned to HKUST as an Associate Professor.

Prof. Zhai’s research focuses on the regulation of genetic and epigenetic inheritance. One of his previous works (Cell 2023) was recognized as one of the Top 10 Scientific Advances in China for 2023 (2023年度中國科學十大進展). Prof. Zhai is also the recipient of the 2024 National Natural Science Funds for Distinguished Young Scholar (2024年度國家傑出青年科學家基金).

Research Question

Molecular mechanisms of eukaryotic DNA/chromatin replication

DNA replication is one of the most fundamental cellular processes, governing the billions of cell divisions from a single fertilized egg to develop into a full-grown human. Every step of the DNA replication process is tightly regulated to ensure that the genome is faithfully duplicated with each cell division. When errors occur, they can have catastrophic consequences, as these mistakes may be amplified and accumulated through DNA replication during development. It is not surprising that DNA replication is closely linked to human diseases, including cancer, aging, and genetic disorders.

During the S phase of the cell division cycle, the replisome–the machinery responsible for DNA replication–can travel hundreds of kilobases without detaching while navigating DNA wrapped in histone octamers, known as nucleosomes. As DNA replication occurs in a context of chromatin, parental nucleosomes bearing epigenetic marks are disrupted ahead of each replication fork to allow for duplex DNA unwinding and subsequent DNA synthesis.

Currently, the detailed molecular mechanisms regulating replication initiation are not yet fully understood in eukaryotes. In addition, how epigenetic information encoded by histone modifications is inherited through chromatin replication remains a mystery.

Research Approach

Prof. Zhai’s lab employs a variety of techniques, including cryo-electron microscopy (cryo-EM), chemical biology, biochemistry, and genomics, to gain deeper insights into the molecular mechanisms underlying large macromolecular complexes involved in DNA/chromatin replication and related DNA/chromatin-centric processes in both yeast and human systems.

Representative Publications

1. Li, N., Gao, Y., Zhang, Y., Yu, D., Lin, W., Feng, J., Li, J., Xu, Z., Zhang, Y., Dang, S., Liu, Y., Zhou, K., Tye, B.^*, Li, Q.^*, Gao, N.^*, Zhai, Y.^* (2024) Parental histone transfer caught at the replication fork. Nature, 627, 890-897
2. Wu, Y., Zhang, Q., Lin, Y., Lam, W., Zhai, Y.^* (2024) Replication licensing regulated by an intrinsically disordered region of origin recognition complex. Nature Communications 15:8039
3. Luo, J., Lam, W., Yu, D., Chao, V., Zopfi, M., Khoo, C., Liu, Z., Li, X.D., Zheng, C., Zhai, Y.^*, Ti, S.^* (2024) Tubulin acetyltransferases access and modify the microtubule luminal K40 residue via anchors in taxine-binding pockets. Nature Structural & Molecular Biology https://doi.org/10.1038/s41594-024-01406-3
4. Li, J., Dong, J., Wang, W., Yu, D., Fan, X., Hui, Y., Lee, C., Lam, H., Alary, N., Yang, Y., Zhang, Y., Zhao, Q., Chen, C.^*, Tye, B.^*, Dang, S.^*, Zhai, Y.^* (2023) The Human Pre-replication Complex is an Open Complex. Cell 186, 1-14
5. Lin, J., Wu, Y., Tian, G., Yu, D., Yang, E., Lam, W., Dang, S., Bao, X.^*, Wong J.^*, Zhai, Y.^*, Li X.^* (2023) Menin ‘reads’ H3K79me2 mark in a nucleosomal context. Science 379, 717-723
6. Xu, Z., Feng, J., Yu, D., Huo, Y., Ma, X., Lam, W., Liu, Z., Li, X., Ishibashi, T., Dang, S.^*, Zhai, Y.^* (2023) Synergism between CMG Helicase and Leading Strand DNA Polymerase at Replication Fork. Nature Communications 14: 5849
7. Cheng, J., Li, N., Huo, Y., Tye, B.^*, Gao, N.^*, Zhai, Y.^* (2022) Structural Insight into the MCM double hexamer activation by Dbf4-Cdc7 kinase. Nature Communications 13:1396
8. Lee, S., Cheung, M., Zhao, Y., Lam, W., Ho, V., Rohs, R., Zhai, Y.^*, Leung, D.^*, Tye, B.^* (2021) Humanizing the Yeast Origin Recognition Complex. Nature Communications 12, 33
9. Cheng, J., Li, N., Wang, X., Hu, J., Zhai, Y., Gao, N. (2020) Structural insight into the assembly and conformational activation of autoinhibited human origin recognition complex. Cell Discovery 6, 88
10. Li, N.^, Lam, W.^, Zhai, Y.^^*, Cheng, J.^, Cheng, E., Zhao, Y., Gao, N.^*, Tye, B.^* (2018) Structure of the origin recognition complex bound to DNA replication origin. Nature 559, 217-222 ^co-first authors
11. Zhai, Y.^*, Li, N., Huang, X., Gao, N.^*, Tye, B.^* (2017) Unique roles played by each of the non-identical MCM subunits in DNA Replication Licensing. Molecular Cell 67, 168-179
12. Zhai, Y., Cheng, E., Wu, H., Li, N., Yung, P., Gao, N., Tye, B. (2017) Open-ringed Structure of the Cdt1-MCM Complex as a Precursor of the MCM Double Hexamer. Nature Structural & Molecular Biology 24, 300-308
13. Li, N.^, Zhai, Y.^^*, Zhang, Y., Yang, M., Lei, J., Tye, B.^*, Gao, N.^* (2015) Structure of the Eukaryotic Minichromosome Maintenance Complex at 3.8 Å. Nature 524, 186–191

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