SCIENCE AT THE EDGE SEMINAR

Friday, February 2 at 11:30am

Room 1400 Biomedical and Physical Sciences Bldg.

Refreshments at 11:15


Speaker: B. Montgomery Pettitt
         Professor of Chemistry, Computer Science, Physics,
           Biology and Biochemistry
         University of Houston, Houston, TX

Title:   Knots, Loops and Writhes: How Does Topo Undo Them?

Abstract:

Type II topoisomerases resolve problematic DNA topologies such as knots,
catenanes, and supercoils that arise as a consequence of DNA replication
and recombination.  Failure to restore nominal DNA topology prohibits cell
division and can result in cell death or genetic mutation.  Such
catastrophic consequences make topoisomerases an effective target for
antibiotics and anticancer agents.  Despite their biological and clinical
importance, little is understood about how a topoisomerase differentiates
DNA topologies in a molecule that is significantly larger than the
topoisomerase itself.  It has been proposed that type II topoisomerases
recognize angle and curvature between two DNA helices characteristic of
knotted and/or catenated DNA to account for the enzymes preference to
unlink instead of link DNA.  Here we consider mechanism of recognition of
DNA juxtapositions.  We found that despite the large negative
electrostatic potential formed between two juxtaposed DNA helices, a bulk
counterion concentration as small as 50mM provides sufficient
electrostatic screening to prohibit significant interaction beyond an
interhelical separation of 3nm in both hooked and free juxtapositions.
This suggests that instead of electrostatics, other mechanical forces
such as those occurring in anaphase, knots, catenanes, or the writhe of
supercoiled DNA may be responsible for the formation of DNA
juxtapositions and their and recognition by topoisomerase.