Bik Kwoon Yeung Tye (; born c. 1947) is a Chinese-American molecular geneticist and structural biologist. Tye's pioneering work on

eukaryotic DNA replication Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryo ...

led to the discovery of the minichromosome maintenance (MCM) genes in 1984, which encode the catalytic core of the eukaryotic replisome. Tye also determined the first high-resolution structures of both the MCM complex and the Origin Recognition Complex (ORC) in 2015 and 2018. Tye is currently a Professor Emeritus (2015) at

Cornell University Cornell University is a private statutory land-grant research university based in Ithaca, New York. It is a member of the Ivy League. Founded in 1865 by Ezra Cornell and Andrew Dickson White, Cornell was founded with the intention to teach an ...

and a visiting professor at the

Hong Kong University of Science & Technology The Hong Kong University of Science and Technology (HKUST) is a public research university in Clear Water Bay Peninsula, New Territories, Hong Kong. Founded in 1991 by the British Hong Kong Government, it was the territory's third institution ...

. She is married to Henry Sze-Hoi Tye and is the mother of

Kay Tye Kay M. Tye (born c. 1981) is an American neuroscientist and professor and Wylie Vale Chair in the Salk Institute for Biological Sciences. Her research has focused on using optogenetics to identify connections in the brain that are involved in inn ...

and Lynne Tye.

Early life and education

Tye was born and raised in Hong Kong where she attended St. Stephen's Girls’ College from kindergarten through high school. She then obtained a full scholarship to pursue undergraduate studies in chemistry at

Wellesley College Wellesley College is a private women's liberal arts college in Wellesley, Massachusetts, United States. Founded in 1870 by Henry and Pauline Durant as a female seminary, it is a member of the original Seven Sisters Colleges, an unofficial g ...

in Massachusetts, USA and graduated with a Bachelor of Arts in 1969. Upon graduation, Tye moved to California to complete an M.Sc. in biochemistry at the

University of California San Francisco The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It condu ...

(UCSF) supervised by Cho Hao Li (李卓皓). Following her master's in 1971, Tye pursued Ph.D. training in genetics at the

Massachusetts Institute of Technology The Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. Established in 1861, MIT has played a key role in the development of modern technology and science, and is one of the ...

under the joint mentorship of

David Botstein David Botstein (born September 8, 1942) is an American biologist serving as the chief scientific officer of Calico. He served as the director of the Lewis-Sigler Institute for Integrative Genomics at Princeton University from 2003 to 2013, where ...

and Joel Huberman. In 1974, Tye was awarded the

Helen Hay Whitney Helen Julia Hay Whitney (March 11, 1875 – September 24, 1944) was an American poet, writer, racehorse owner/breeder, socialite, and philanthropist. She was a member by marriage of the prominent Whitney family of New York. Early life She was ...

Post-doctoral Research Fellowship with which she pursued further research training in molecular genetics under the supervision of Bob Lehman at

Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is consider ...

until 1977. Her post-doctoral work on DNA replication lead to the discovery of short

Okazaki fragments Okazaki fragments are short sequences of DNA nucleotides (approximately 150 to 200 base pairs long in eukaryotes) which are synthesized discontinuously and later linked together by the enzyme DNA ligase to create the lagging strand during DNA r ...

generated during aberrant DNA repair in E.coli.

Career and research

After Tye's foundational contributions to the field of prokaryotic DNA replication while at

she moved to

Ithaca, New York Ithaca is a city in the Finger Lakes region of New York, United States. Situated on the southern shore of Cayuga Lake, Ithaca is the seat of Tompkins County and the largest community in the Ithaca metropolitan statistical area. It is named a ...

and started her own laboratory at Cornell University in 1977. In her independent career, Tye began forging new discoveries surrounding DNA replication in eukaryotes, an understudied area at the time. Tye took a genetic approach to isolate mutants that regulate DNA replication which led to her identification of the minichromosome maintenance (MCM) genes in yeast in 1984. She specifically identified the MCM2, MCM3, MCM5 and MCM10 genes in yeast. Her findings together with the identification of the origin recognition complex (ORC) by Bell and Stillman in 1992 generated substantial momentum in the field of eukaryotic DNA replication. Tye's contributions to the field continued throughout her tenure at Cornell. Throughout the 1990s, Tye functionally characterized the components of eukaryotic DNA replication machinery. At Cornell, Tye mentored numerous graduate students, was the associate chair of the Department of Biochemistry, Molecular, and Cell Biology, directed the Genetics and Development Graduate Studies Program, and finally received her Emerita status in 2015 for her contributions to the Cornell community. More recently, Tye began a visiting professorship at the

Hong Kong University of Science and Technology The Hong Kong University of Science and Technology (HKUST) is a public research university in Clear Water Bay Peninsula, New Territories, Hong Kong. Founded in 1991 by the British Hong Kong Government, it was the territory's third institution ...

where she began to address a large gap in the field: the lack of high-resolution structures for ORC and MCM. To place genetic and biochemical DNA replication data into structural context, Tye began using

cryogenic electron microscopy Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample so ...

(cryo-EM) to identify the structures of these molecular complexes at near-atomic resolution. She helped determine the high resolution structures of the MCM complexes in 2015 and ORC in 2018.

Selected publications

# Maine, G. T., Sinha, P. & Tye, B. K. Mutants of S. cerevisiae defective in the maintenance of minichromosomes. ''Genetics'' 106, 365-385 (1984). # Sinha, P., Chang, V. & Tye, B. K. A mutant that affects the function of autonomously replicating sequences in yeast. ''J Mol Biol'' 192, 805-814 (1986). # Yan, H., Gibson, S. & Tye, B. K. Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function. ''Genes Dev'' 5, 944-957 (1991). # Yan, H., Merchant, A. M. & Tye, B. K. Cell cycle-regulated nuclear localization of MCM2 and MCM3, which are required for the initiation of DNA synthesis at chromosomal replication origins in yeast. ''Genes Dev'' 7, 2149–2160 (1993). # Lei, M., Kawasaki, Y., Young, M. R., Kihara, M., Sugino, A. & Tye, B. K. Mcm2 is a target of regulation by Cdc7-Dbf4 during the initiation of DNA synthesis. ''Genes Dev'' 11, 3365-3374 (1997). # Homesley, L., Lei, M., Kawasaki, Y., Sawyer, S., Christensen, T. & Tye, B. K. Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins. ''Genes Dev'' 14, 913-926 (2000). # Shima, N., Alcaraz, A., Liachko, I., Buske, T. R., Andrews, C. A., Munroe, R. J., Hartford, S. A., Tye, B. K. & Schimenti, J. C. A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. ''Nat Genet'' 39, 93-98, doi:10.1038/ng1936 (2007). # Eisenberg, S., Korza, G., Carson, J., Liachko, I. & Tye, B. K. Novel DNA Binding Properties of the Mcm10 Protein from Saccharomyces cerevisiae. ''Journal of Biological Chemistry'' 284, 25412-25420, doi:10.1074/jbc.M109.033175 (2009). # Lee, C., Liachko, I., Bouten, R., Kelman, Z. & Tye, B. K. Alternative Mechanisms for Coordinating Polymerase alpha and MCM Helicase. ''Molecular and Cellular Biology'' 30, 423-435, doi:10.1128/Mcb.01240-09 (2010). # Li, N., Zhai, Y., Zhang, Y., Li, W., Yang, M., Lei, J., Tye, B. K. & Gao, N. Structure of the eukaryotic MCM complex at 3.8 A. ''Nature'' 524, 186-191, doi:10.1038/nature14685 (2015). # Zhai, Y., Cheng, E., Wu, H., Li, N., Yung, P. Y., Gao, N. & Tye, B. K. Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer. ''Nat Struct Mol Biol'' 24, 300-308, doi:10.1038/nsmb.3374 (2017). # Li, N., Lam, W. H., Zhai, Y., Cheng, J., Cheng, E., Zhao, Y., Gao, N. & Tye, B. K. Structure of the origin recognition complex bound to DNA replication origin. ''Nature'' 559, 217-222, doi:10.1038/s41586-018-0293-x (2018). # Tye, B. K. The MCM2-3-5 proteins: are they replication licensing factors? ''Trends Cell Biol'' 4, 160-166 (1994). # Tye, B. K. MCM proteins in DNA replication. ''Annu Rev Biochem'' 68, 649-686, doi: 10.1146/annurev.biochem.68.1.649 (1999). # Tye, B. K. Insights into DNA replication from the third domain of life. ''P Natl Acad Sci USA'' 97, 2399–2401, doi:DOI 10.1073/pnas.97.6.2399 (2000). # Tye, B. K. & Sawyer, S. The hexameric eukaryotic MCM helicase: Building symmetry from nonidentical parts. ''Journal of Biological Chemistry'' 275, 34833-34836, doi:DOI 10.1074/jbc.R000018200 (2000). # Lei, M. & Tye, B. K. Initiating DNA synthesis: from recruiting to activating the MCM complex. ''J Cell Sci'' 114, 1447–1454 (2001). # Zhai, Y., Li, N., Jiang, H., Huang, X., Gao, N. & Tye, B. K. Unique Roles of the Non- identical MCM Subunits in DNA Replication Licensing. ''Mol Cell'' 67, 168-179, doi: 10.1016/j.molcel.2017.06.016 (2017).

Personal life

Tye is married to Henry Sze-Hoi Tye. Tye is the mother of

, professor of systems neurobiology at the Salk Institute for Biological Studies, and Lynne Tye, web developer and founder of Key Values.

References

{{DEFAULTSORT:Tye, Bik Kwoon Stanford University alumni Hong Kong scientists Cornell University faculty American people of Chinese descent Chinese geneticists Wellesley College alumni University of California, San Francisco alumni Massachusetts Institute of Technology School of Science alumni 20th-century Chinese scientists American women biologists 20th-century American biologists 1947 births Living people 21st-century American biologists Hong Kong emigrants to the United States Women geneticists 21st-century Chinese scientists 21st-century American women scientists 20th-century American women scientists American women academics