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Bik Kwoon Tye

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Bik K Tye
Bik Kwoon Tye
Alma materWellesley College (B.A)

University of California, San Francisco (UCSF) (M.Sc.)

Massachusetts Institute of Technology (Ph.D.)
Known forOkazaki fragment generation during aberrant DNA repair in E. coli, Minichromosome maintenance genes (MCM) in yeast, High-resolution structures of MCM complexes and origin recognition complex (ORC)
SpouseHenry Sze-Hoi Tye
Children2
AwardsHelen Hay Whitney Postdoctoral Research Fellowship (1974–1977). Elected to the National Academy of Sciences (2023).
Scientific career
FieldsMolecular Genetics, Structural Biology
InstitutionsCornell University, Hong Kong University of Science & Technology
Doctoral advisorDavid Botstein and Joel Huberman

Bik Kwoon Yeung Tye (Chinese: 戴楊碧瓘; born c. 1947) is a Chinese-American molecular geneticist and structural biologist. Tye's pioneering work on eukaryotic DNA replication led to the discovery of the minichromosome maintenance (MCM) genes in 1984,[1] which encode the catalytic core of the eukaryotic replisome. Tye also determined the first high-resolution structures of both the MCM complex[2] and the Origin Recognition Complex (ORC)[3] in 2015 and 2018. Tye is currently a Professor Emeritus (2015) at Cornell University.[4] She is married to Henry Sze-Hoi Tye and is the mother of Kay Tye[5] and Lynne Tye.[6]

Early life and education

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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 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 (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 under the joint mentorship of David Botstein and Joel Huberman. In 1974, Tye was awarded the Helen Hay Whitney Post-doctoral Research Fellowship with which she pursued further research training in molecular genetics under the supervision of Bob Lehman at Stanford University until 1977. Her post-doctoral work on DNA replication lead to the discovery of short Okazaki fragments generated during aberrant DNA repair in E.coli.

Career and research

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After Tye's training in the field of prokaryotic DNA replication at Stanford University, she moved to Ithaca, New York and started her own laboratory at Cornell University in 1977.[7] In her independent career, Tye began forging new discoveries surrounding DNA replication in eukaryotes, an understudied area at the time.[8] 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.[9] Her findings together with the identification of the origin recognition complex (ORC) by Bell and Stillman in 1992[10] generated substantial momentum in the field of eukaryotic DNA replication.

Tye's contributions to the field continued during her tenure at Cornell. Throughout the 1990s, Tye functionally characterized the components of eukaryotic DNA replication machinery.[11][12] 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.

In 2011, Tye began a visiting professorship at the Hong Kong University of Science and Technology, where she addressed a large gap in the field: the lack of high-resolution structures for DNA replication complexes.[13] To place genetic and biochemical DNA replication data into physical context, Tye and collaborators used cryogenic electron microscopy (cryo-EM) to determine the high resolution structures of numerous DNA replication complexes, including the yeast and human pre-replication complexes, yeast ORC, Dbf4-Cdc7 kinase (DDK)-MCM complex, and the replisome engaged in parental histone transfer.

Selected publications

1. Tye BK. Four decades of eukaryotic DNA replication: from yeast genetics to high-resolution cryo-EM structures of the replisome. PNAS 121(42) e2415231121. (2024) 2. Li N, Gao Y, Zhang Y, Yu D, Lin J, Feng J, Li J, Xu Z, Zhang Y, Dang S, Zhou K, Liu Y, Li XD, Tye BK, Li Q, Gao N, Zhai YL. Parental histone transfer caught at the replication fork. Nature 627:8005, 890-897. (2024) 3. Li J, Dong J, Wang W, Yu D, Fan X, Hui YC, Lee CSK, Lam WH, Alary N, Yang Y, Zhang Y, Zhao Q, Chen CL, Tye BK, Dang S, Zhai Y. The human pre-replication complex is an open complex. Cell 186:1, 98-111. (2023) 4. Cheng J, Li N, Huo Y, Dang S, Tye BK, Gao N, Zhai Y. Structural Insight into the MCM Double Hexamer Activation by Dbf4-Cdc7 Kinase. Nat Commun 13:1396. (2022) 5. Lee CSK, Cheung MF, Li J, Zhao Y, Lam WH, Ho V, Rohs R, Zhai Y, Leung D, Tye BK. Humanizing the Yeast Origin Recognition Complex. Nat Commun 12:33. (2021) 6. Li, N, Lam WH, Zhai Y, Cheng J, Zhao Y, Gao, N and Tye, BK. Structure of the Origin Recognition Complex Bound to DNA Replication Origin. Nature 559:217-222. (2018) 7. Li, N., Zhai, Y, Zhang Y., Li, W., Yang, M., Lei, J., Tye, BK, Gao, N. Structure of the Eukaryotic Minichromosome Maintenance Complex at 3.8Å. Nature 524:186-91. (2015) 8. Maine, G., Sinha, P. and Tye, B.K. Mutants of S. cerevisiae defective in the maintenance of minichromosomes. Genetics 106: 365–385. (1984) 9. Chan, C.S.M. and Tye, B.K. Organization of DNA sequences and replication origins at yeast telomeres. Cell 33: 563–573. (1983) 10.Chan, C.S.M. and Tye, B.K. Autonomously replicating sequences in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 77: 6329–6333. (1980)


References

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  1. ^ Tye, Bik-Kwoon; Sinha, Pratima; Maine, Gregory T. (1984-03-01). "Mutants of S. Cerevisiae Defective in the Maintenance of Minichromosomes". Genetics. 106 (3): 365–385. doi:10.1093/genetics/106.3.365. ISSN 0016-6731. PMC 1224244. PMID 6323245.
  2. ^ Gao, Ning; Tye, Bik-Kwoon; Lei, Jianlin; Maojun Yang; Li, Wanqiu; Zhang, Yixiao; Zhai, Yuanliang; Li, Ningning (August 2015). "Structure of the eukaryotic MCM complex at 3.8 Å". Nature. 524 (7564): 186–191. Bibcode:2015Natur.524..186L. doi:10.1038/nature14685. ISSN 1476-4687. PMID 26222030. S2CID 4468690.
  3. ^ Tye, Bik-Kwoon; Gao, Ning; Zhao, Yongqian; Cheng, Erchao; Cheng, Jiaxuan; Zhai, Yuanliang; Lam, Wai Hei; Li, Ningning (July 2018). "Structure of the origin recognition complex bound to DNA replication origin". Nature. 559 (7713): 217–222. Bibcode:2018Natur.559..217L. doi:10.1038/s41586-018-0293-x. ISSN 1476-4687. PMID 29973722. S2CID 49577101.
  4. ^ "Emeriti Faculty | Department of Molecular Biology and Genetics". mbg.cornell.edu. Retrieved 2019-08-04.
  5. ^ Schaffer, Amanda. "Homing in on how the brain helps us seek pleasure and avoid pain". MIT Technology Review. Retrieved 2019-08-23.
  6. ^ "A 70yo's secret to a full and happy life". Keyv values blog. Retrieved 21 November 2019.
  7. ^ Tye, Bik Kwoon (2009-02-01). "Memories of Ray Wu by a Colleague". Science in China Series C: Life Sciences. 52 (2): 133–134. doi:10.1007/s11427-009-0027-2. ISSN 1862-2798. PMID 19277524. S2CID 28938295.
  8. ^ Kelly, Thomas (2017). Masai, Hisao; Foiani, Marco (eds.). Historical Perspective of Eukaryotic DNA Replication. Advances in Experimental Medicine and Biology. Vol. 1042. Springer Singapore. pp. 1–41. doi:10.1007/978-981-10-6955-0_1. ISBN 9789811069550. PMID 29357051. {{cite book}}: |work= ignored (help)
  9. ^ Maine, G. T.; Sinha, P.; Tye, B. K. (March 1984). "Mutants of S. cerevisiae defective in the maintenance of minichromosomes". Genetics. 106 (3): 365–385. doi:10.1093/genetics/106.3.365. ISSN 0016-6731. PMC 1224244. PMID 6323245.
  10. ^ Bell, S. P.; Stillman, B. (1992-05-14). "ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex". Nature. 357 (6374): 128–134. Bibcode:1992Natur.357..128B. doi:10.1038/357128a0. ISSN 0028-0836. PMID 1579162. S2CID 4346767.
  11. ^ Yan, H.; Gibson, S.; Tye, B. K. (June 1991). "Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function". Genes & Development. 5 (6): 944–957. doi:10.1101/gad.5.6.944. ISSN 0890-9369. PMID 2044961.
  12. ^ Yan, H.; Merchant, A. M.; Tye, B. K. (November 1993). "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 & Development. 7 (11): 2149–2160. doi:10.1101/gad.7.11.2149. ISSN 0890-9369. PMID 8224843.
  13. ^ "香港科技大學賽馬會高等研究院 -". ias.ust.hk. Retrieved 2019-08-14.
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