The Department of Pharmacology and Toxicology invites you to join us as we host Dr. Valérie Lamour, Associate Professor in the Department of Integrated Structural Biology, Institute of Genetics, Molecular and Cellular Biology (IGBMC) at Strasbourg University, Strasbourg, France. 

Dr. Lamour will be presenting “A Structural Perspective on the Regulation of DNA Topology.”

Presentation Abstract:

DNA topoisomerases are essential enzymes that regulate DNA topology in all organisms. The human topoisomerase IIα isoform is a prime target for antineoplastic compounds used in cancer therapy that form ternary cleavage complexes with the DNA. Despite extensive studies, structural information on this large dimeric assembly was initially limited to the catalytic domains, hindering the exploration of allosteric mechanism governing the enzyme activities and the response to drugs. Building up on our experience with the homologous bacterial enzymes, we have determined the molecular architecture of the entire human Topo IIα nucleoprotein complex using cryo-electron microscopy. Our data unveils the molecular determinants that fine tune the allosteric connections between the catalytic domains, and with the isoform-specific C-terminal domain which modulates the enzyme activities.