Chem 550 Lab

DNA Manipulation Machinery Structure, Function and Inhibition

Research ImageOur group has a long-standing interest in the manner in which DNA and other polynucleic acids are managed and manipulated within cells.

Published work in this area include several studies on human DNA topoisomerases, which are also the sole targets of the camptothecin class of potent anticancer drugs, as well as the bacterial conjugative DNA transfer process that moves antibiotic resistant genes between neighboring microbial cells.

In addition, our team has investigated the Werner syndrome helicase-exonuclease and the pre-mRNA processing machinery.

Our group pursues research to understand the manner in which DNA and other poly-nucleic acids are managed and manipulated within the cells. Researchers in our laboaratory have investigated DNA topoisomerases and helicases, as well as conjugative relaxases.

Some representative publications include:

 

Lujan, S.A., Guogas, L.M., Ragonese, H., Matson, S.W., and Redinbo, M.R. (2007).
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
Proceedings of the National Academy of Sciences USA, 104, 12282-12287.

Chrencik, J.E., Staker, B.L., Burgin, A.B., Pourquier, P., Pommier, Y., Stewart, L., and Redinbo, M.R. (2004).
Mechanisms of camptothecin resistance by human topoisomerase I mutations.
Journal of Molecular Biology, 339, 773-784.

Lesher, D.-T.T., Pommier, Y., Stewart, L., and Redinbo, M.R. (2002).
8-oxoguanine rearranges the active site of human topoisomerase I.
Proceedings of the National Academy of Sciences USA, 99, 12102-12107.

Redinbo, M.R., Stewart, L., Kuhn, P., Champoux, J.J., and Hol, W.G.J. (1998).
Crystal structures of human topoisomerase I in covalent and non-covalent complexes with DNA.
Science, 279, 1504-1513.