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A collaboration led by the Hong Kong University of Science and Technology (HKUST), the University of Hong Kong (HKU) and other institutions to uncover a new mechanism for the initiation of DNA replication has been named one of the world’s top 10 scientific advances. In 2023, China will be targeted, making it the only research project originating from Hong Kong included in the list.
Organized by the National Natural Science Foundation of China, “China’s Top 10 Scientific Progress in 2023” is co-sponsored by the High-Technology Research and Development Center and the Center for Science Communication and Achievement Transformation, with the cooperation of the following five journals: China Basic Science, Science and Technology Review, Bulletin of the Chinese Academy of Sciences, Chinese Science Foundation, and Bulletin of Science. These 10 advances were carefully selected by thousands of experts from the Chinese Academy of Sciences, the Chinese Academy of Engineering, and other institutions. Its purpose is to promote the advancement of cutting-edge and innovative research in China and encourage more researchers to engage in basic research. The event also aims to foster a favorable national climate for scientific inquiry by deepening public understanding, interest, and support for science.
This prestigious honor was awarded to a team including Professor ZHAI Yuanliang from the School of Biological Sciences, The University of Hong Kong, Professor DANG Shangyu, Assistant Professor and Professor TYE Bik-Kwoon from the HKUST Life Sciences Division (LIFS). Senior member of HKUST Institute for Advanced Study (IAS). The breakthrough discovery of a new mechanism of the human pre-replication complex (Pre-RC) in the control of DNA replication initiation is acknowledged. The atomic resolution structure of human Pre-RC provides detailed and important information for devising novel and effective anticancer strategies with the ability to selectively kill cancer cells.
Professor Zhai Yuanliang from HKU said, “This recognition is a great honor for our research team and shows that our research is highly regarded in the scientific community.” “Our knowledge of how DNA is copied is still quite limited. Previous studies in certain yeast species have provided some insights, but this process has not been shown in humans. There is still much we don’t know about how this happens in our cells. “Discoveries in this field will help us understand how DNA is copied by our replication machinery.” Every new development is a major breakthrough. The knowledge gained from our research not only improves our understanding of the fundamental processes of life, but also provides important insights into diseases such as cancer. , which can help find new treatments.”
Professor Dang Shangyu from HKUST said: “Increasing the specificity of chemotherapeutic drugs has always been an important consideration in the development of anti-cancer compounds. We are delighted to receive national recognition for the groundbreaking results of our research. We are particularly pleased that all structural work on the project involving low temperatures, sample preparation, cryo-EM data collection and processing was carried out at the HKUST Biological Cryo-EM Center, which is a state-of-the-art We would like to express our deepest gratitude to the Lo Kwee Seong (LKS) Foundation for their generous support in establishing this facility. At HKUST, we have already made several breakthrough discoveries in our research since our establishment in 2019. We look forward to continuing our research in this field and building new hope in cancer treatment.”
Research background
DNA is the blueprint of life. It is present in every cell. Its double structure with complementary notation shows how it can be replicated. First, it must be separated into single strands and copied accurately. The history of DNA replication research can be traced back to the 1950s, when Professor Arthur Kornberg discovered an enzyme system in extracts of Escherichia coli, which ultimately won him the Nobel Prize. However, in the absence of high-resolution structures, advances in DNA replication research have lagged behind those achieved in the study of other macromolecular machines, such as the ribosome and RNA polymerase.
Professor Tye Bik-Kwoon, who joined HKUST in 2011, initially sought to overcome these hurdles by collaborating with the Peking University team led by Professor GAO Ning and with Professor Zhai, who completed his PhD at HKUST before becoming HKUST. did. IAS Junior Fellow. Together, they made a series of breakthrough discoveries, including the determination of the cryo-electron microscopy (cryo-EM) structure of the yeast MCM2-7 double hexamer (DH) and the yeast-origin recognition complex, and in 2015 and he published it in Nature magazine in 2018. When HKUST’s cryo-EM facility became available and Professor Dunn joined HKUST in 2019, his research laid the foundation for current research on the structure of the human pre-replication complex.
This study, one of the top 10 scientific advances in China in 2023, determined the cryo-EM structure of human Pre-RC formed by loading MCM2-7 DH onto the original DNA at 2.59 Å . This structure shows how the MCM2-7 complex destabilizes DNA and precisely causes the first unwinding of the DNA duplex at the junction of two bound she MCM2-7 hexamers. can be clearly understood. Additionally, the research team discovered that the MCM2-7 DH complex is loaded into DNA at numerous sites throughout the human genome. Importantly, these sites are mutually exclusive with loci of active transcription to minimize interference between DNA replication and transcription. Furthermore, once the initial open structure is disrupted, the MCM2-7 DH complex is unable to assemble onto DNA, completely inhibiting DNA replication initiation. This study provides a detailed understanding of the high-resolution structure and mechanism of human Pre-RC. This knowledge could be used in the future to develop non-toxic anti-cancer drugs. The study was published in the top international scientific journal Cell in January 2023. (Click here for link)
Introductory video:
About Hong Kong University of Science and Technology
The Hong Kong University of Science and Technology (HKUST) (https://hkust.edu.hk/) is a world-class, research-intensive university with a focus on science, engineering and business as well as the humanities and social sciences. HKUST offers an international campus and a comprehensive and interdisciplinary pedagogy to develop well-rounded graduates with a global perspective, strong entrepreneurial spirit, and innovative thinking. More than 80% of our research outputs were rated as “internationally excellent” or “world-leading” in the Hong Kong University Grants Commission’s 2020 Research Assessment Exercise. We were ranked 2nd in the Times Higher Education Young University Rankings 2023, and our graduates were ranked 29th in the world and among the top universities in Asia in the 2023 Global Employability University Rankings. . As of September 2023, HKUST members have established 1,747 active startup companies. It has generated over HK$400 billion in economic impact, including 9 unicorns and 13 exits (IPO or M&A). InvestHK cites the 2021 QS World University Rankings by subject, demonstrating the performance of five local universities in the world’s top 100 in several innovation-focused fields, among which HKUST ranks in four subjects in engineering and materials science. was ranked top.
About the University of Hong Kong
Founded in 1911, the University of Hong Kong (HKU) (www.hku.hk) is Hong Kong’s first and oldest higher education institution. For more than a century, universities have been dedicated to creating knowledge, providing education, and serving society. Today, HKU has a global reputation as a research-driven university with 10 faculties. HKU has a proud track record of academic recognition in the field of research through honors and awards received from both local and international organizations. The University strives to attract and develop outstanding scholars through excellence and innovation in research and knowledge exchange activities. Its research areas cover a wide range of issues with the aim of benefiting industry, businesses and communities. Known as Asia’s Global University, HKU partners with prestigious universities and research institutes around the world, bringing together experts from a variety of fields. Clarivate’s 2023 Highly Cited Researchers list includes 51 scholars, ranking him 13th in the world among all institutions. HKU pursues excellence in teaching and learning across a wide range of disciplines and specialties. Through a comprehensive curriculum design and award-winning teaching and learning resources and support, HKU students fully develop their intellectual and personal strengths while gaining lifelong learning opportunities to contribute to their communities. can be extended to
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