E-mail: lslhj@life.nthu.edu.tw
Reserach
DNA topoisomerase II is an essential nuclear enzyme which regulates the superhelicity of DNA. The cellular events that specifically required DNA topoisomerase II are believed: the segregation of resultant daughter molecules after DNA replication; segregation of sister chromatids during meiosis; relaxation of DNA supercoils during transcription; DNA recombination and the condensation of chromosome at the onset of mitosis. Beside its enzymatic properties, topoisomerase II is one of the structural components of chromosome scaffold and nuclear matrix. Recent studies have demonstrated that the interactions between nuclear matrix and matrix attached region (MAR) DNA fragments may involve with the on/off of transcription and replication. In addition, topoisomerase II is a good target for several anti-tumor drugs. Then, to develop new topoisomerase II inhibitor is a promising strategy for cancer therapy.
We purified topoisomerase I from chicken RBC and topoisomerase II from chicken embryo as well as porcine spleen, and clarified the cleavage behavior and enzymatic properties of these enzymes.
Beside these experiments, we found a new topoisomerase II inhibitor --- With angulatin A in cooperation with professor Chen C-M in the department of chemistry.
The ongoing projects and the projects planned to start from 1994:
1. Characterization of porcine murine spleen and liver MAR DNA fragments, and their classification by topoisomerase II cutting pattern.
2. The tissue specific interaction between MAR DNA and nuclear matrix. Previously, we discovered that some porcine spleen MAR DNA bind differently to liver matrix proteins compared with that of its homologous spleen matrix proteins.
3. Large scale purification of human topoisomerase II from S. cerevisiae host cell using the Topo II cDNA from professor J.C. Wang, Department of Molecular Biology & Biochemistry, Harvard Univ.
4. Developement of a simple and rapid screening method for topoisomerase II inhibitor.
5. Study of the binding characters between MAR DNA and matrix protein.
6. Isolation and sequencing of human MAR DNA.
Selected Publications
- Juang, J.-K. and Liu, H.-J. Biochem. Biophys. Res. Commun. 146, 1458-1464 (1987).
- Juang, J.-K., Huang, H.-W., Chen, C.-M and Liu, H.-J. Biochem. Biophys. Res. Commun. 159, 1128-1134 (1989).
- Lee, W.-C., Lin, K.-Y., Chen, C.-M., Chen, Z.-T, Liu, H.-J. and Lai, Y.-K. J. Cell. Physiol. 149, 66-76 (1991).
- Huang, H.-W., Juang, J.-K. and Liu, H.-J. Nuclein Acids Res. 20, 467-473 (1992).
