Institute of Biological Chemistry, Academia Sinica

Research

There are two main research subjects in the Tsai lab. One focuses on the protein-phosphoprotein interaction related to DNA damage response and cancer signaling, particularly those involving phosphothreonine signaling mediated by the FHA domain. The specific systems under study include human CHK2, MDC1, Ki67, NIFK, TIFA, and yeast Rad53 kinase and Dun1 kinase. A particular emphasis is on the mechanism of activation of checkpoint kinases in vivo. The other subject is the catalytic mechanism, structure, and function of DNA polymerase involved in DNA repair. These include human DNA polymerases beta and lamda, and African swine fever virus (ASFV) DNA polymerase X. A particular emphasis is on the mechanistic differences between high-fidelity and low-fidelity DNA polymerases. Recently, with the support of Taiwan Protein Project, we have been actively engaged in using the time-resolved serial femtosecond X-ray crystallography to study the mechanism of DNA photolyases, and in applying cryo-EM to mechanistic enzymology.

Degrees and Positions Held

• 1978   Ph.D, Biochemistry & Medicinal Chemistry, Purdue University
• 1972   B.S., Chemistry, National Taiwan University, Taipei

• 2020 – present   Distinguished Visiting Chair, Institute of Biological Chemistry, Academia Sinica
• 2008 – 2020   Distinguished Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 2012   Academician, Academia Sinica
• 2010 – 2016   Associate Editor, Biochemistry
• 2008 – 2014   Director, Institute of Biological Chemistry, Academia Sinica
• 2006 – 2008   Acting Director, Institute of Biological Chemistry, Academia Sinica
• 2005 – 2008   Director, Division of Functional Genomics, Genomics Research Center
• 2003 – 2008   Director, National Research Program for Genomic Medicine Core Facility Office
• 1995 – 2003   Director, Chemistry/Biology Interface Training Program, OSU
• 1993 – 2007   Director, Office of Research Campus Chemical Instrument Center, The Ohio State University
• 1992 – 1992   Elected Fellow, American Association for the Advancement of Science (AAAS)
• 1992 – 1992   Distinguished Scholar Award, Ohio State University
• 1985 – 1990   Camille and Henry Dreyfus Teacher-Scholar
• 1985 – 1985   Faculty Research Award, Ohio State Chapter of Sigma Xi
• 1983 – 1985   Alfred P. Sloan Fellow
• 1981 – 2006   Kimberly Professor of Chemistry and Professor of Biochemistry, The Ohio State University (starting as Assistant Professor)

Selected Publications

Visualizing the DNA repair process by a photolyase at atomic resolution. 
Maestre-Reyna M, Wang PH, Nango E, Hosokawa Y, Saft M, Furrer A, Yang CH, Gusti Ngurah Putu EP, Wu WJ, Emmerich HJ, Caramello N, Franz-Badur S, Yang C, Engilberge S, Wranik M, Glover HL, Weinert T, Wu HY, Lee CC, Huang WC, Huang KF, Chang YK, Liao JH, Weng JH, Gad W, Chang CW, Pang AH, Yang KC, Lin WT, Chang YC, Gashi D, Beale E, Ozerov D, Nass K, Knopp G, Johnson PJM, Cirelli C, Milne C, Bacellar C, Sugahara M, Owada S, Joti Y, Yamashita A, Tanaka R, Tanaka T, Luo F, Tono K, Zarzycka W, Müller P, Alahmad MA, Bezold F, Fuchs V, Gnau P, Kiontke S, Korf L, Reithofer V, Rosner CJ, Seiler EM, Watad M, Werel L, Spadaccini R, Yamamoto J, Iwata S, Zhong D, Standfuss J, Royant A, Bessho Y, Essen LO, Tsai MD 
Science (2023)

An ATP-sensitive phosphoketolase regulates carbon fixation in cyanobacteria. 
Lu KJ, Chang CW, Wang CH, Chen FY, Huang IY, Huang PH, Yang CH, Wu HY, Wu WJ, Hsu KC, Ho MC, Tsai MD, Liao JC 
Nature Metabolism (2023)

Enzymology and Dynamics by Cryogenic Electron Microscopy. 
Tsai MD, Wu WJ, Ho MC 
Annual Review of Biophysics (2022)

Serial crystallography captures dynamic control of sequential electron and proton transfer events in a flavoenzyme. 
Maestre-Reyna M, Yang CH, Nango E, Huang WC, Ngurah Putu EPG, Wu WJ, Wang PH, Franz-Badur S, Saft M, Emmerich HJ, Wu HY, Lee CC, Huang KF, Chang YK, Liao JH, Weng JH, Gad W, Chang CW, Pang AH, Sugahara M, Owada S, Hosokawa Y, Joti Y, Yamashita A, Tanaka R, Tanaka T, Luo F, Tono K, Hsu KC, Kiontke S, Schapiro I, Spadaccini R, Royant A, Yamamoto J, Iwata S, Essen LO, Bessho Y, Tsai MD 
Nature Chemistry (2022)

Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures. 
Luo SC, Yeh HY, Lan WH, Wu YM, Yang CH, Chang HY, Su GC, Lee CY, Wu WJ, Li HW, Ho MC, Chi P, Tsai MD 
Nature Communications (2021)

Temperature-Resolved Cryo-EM Uncovers Structural Bases of Temperature-Dependent Enzyme Functions. 
Chen CY, Chang YC, Lin BL, Huang CH, Tsai MD 
Journal of the American Chemical Society (2019)

Human DNA Polymerase μ Can Use a Noncanonical Mechanism for Multiple Mn²⁺-Mediated Functions. 
Chang YK, Huang YP, Liu XX, Ko TP, Bessho Y, Kawano Y, Maestre-Reyna M, Wu WJ, Tsai MD 
Journal of the American Chemical Society (2019)

Publication List