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.
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)
Preparation of High-Temperature Sample Grids for Cryo-EM.
Chang YC, Chen CY, Tsai MD
Journal of Visualized Experiments (2021)
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)
Use of Cryo-EM To Uncover Structural Bases of pH Effect and Cofactor Bispecificity of Ketol-Acid Reductoisomerase.
Chen CY, Chang YC, Lin BL, Lin KF, Huang CH, Hsieh DL, Ko TP, Tsai MD
Journal of the American Chemical Society (2019)