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TSAI-KUN, LI (李財坤)
by chang shu-wen, 2011-01-24 11:37, Views(1002)
ASSOCIATE PROFESSOR

DNA TOPOLOGY AND ITS
BIOLOGICAL IMPLICATIONS,
TOPOISOMERASE AND TARGETING
DRUGS, DNA DAMAGE AND REPAIR,
CARCINOGENESIS
 
The research conducted in my laboratory combines cellular, molecular and biochemical approaches toward investigating the following interrelated programs of research: (1) roles of topoisomerases in chromatin organization; (2) studies on topoisomerase-mediated DNA damage (3) gene regulation and genome stability during tumorigenesis. Topoisomerases are ubiquitous, essential nuclear enzymes that participate in regulating different DNA topological states by transient breakage and rejoining of DNA. Current research efforts focus on involvements of topoisomerases in the generation and regulation on transcription associated R-loop, in the higher-order eu- and pro-karyotic chromatin structure (topoisomerase II) and in suppressing tumorigenesis (topoisomerase IIIalpha). Moreover, due to the delicate act of breaking/rejoining DNA, topoisomerases are vulnerable while performing the enzymatic reaction. In agreement, topoisomerase I and II have also been firmly established as effective molecular targets for antibiotics (e.g. quinolones) as well as anti-tumor drugs (e.g. camptothecins). Thus, our lab is also interested in defining molecular determinants for topoisomerase drugs. We study the roles of topoisomerase-targeting in different physiological and pathological conditions (e.g. acidic stress) and processing events downstream of enzyme-capped DNA damage. New generation of topoisomerase drugs with better efficacy and reduced side-effects were also under development. Finally, post-translational modifications of topoisomerases including ubiquitination, proteolysis, SUMOylation and ISGylation, as well as their roles in cellular functions have also been studied.
• Huang TH, Chen HC, Chou SM, Yang YC, Fan JR, and Li T-K Cellular processing determinants for the activation of damage signals in response to topoisomerase I-linked DNA breakage. Cell Research
2010;20(9):1060-75.
• Hsu YH, Chung MW, and Li T-K Distribution o gyrase and topoisomerase IV on bacterial nucleoid: implications for nucleoid organization. Nucleic Acid Research 2006;34(10):3128-38.
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