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.