DNA topoisomerases (topos) solve the topological problems inherent to the double-helical structure of the DNA. Such problems must be solved in order for vital cellular processes to be completed, and to maintain the integrity of the genome. Professor Marc Drolet, of the Department of Microbiology and Immunology, University of Montreal, will give a presentation.

Type I topos cut one DNA strand and either use a strand passage (1A) or a rotation mechanism (1B) to alter the topology of DNA. Type II enzymes cut two DNA strands and use a strand passage mechanism. Of all topoisomerases, enzymes of the type (1A) family are the most ancient and the only ubiquitous. They are classified in two subfamilies, topo I and topo III, respectively found in bacteria only and in organisms from the three domains of life.

The prototype enzymes are topo I (topA) and topo III (topB) from Escherichia coli. Recent findings strongly suggest that gene duplications that led to topo I and III occurred in LUCA (Last Universal Common Ancestor) for the three domains of life. E. coli cells lacking both topo I and III (double topA topB null mutants) are very sick and display phenotypes that are not observed for single topA and topB null mutants. This suggests that both enzymes share a common function that may have been present early in the evolution.

Dr. Drolet will present results strongly suggesting that this function is the inhibition of unscheduled replication from R-loops, to maintain the stability of the genome. Furthermore, he will present models explaining how topo I and III can regulate this type of replication to avoid chromosome segregation problems and genomic instability.

Co-sponsored by the Biomolecular Sciences Institute and the Department of Chemistry and Biochemistry