Speaker
Prof.
Hue Sun Chan
(Departments of Biochemistry, of Molecular Genetics, and of Physics, University of Toronto)
Description
Closed DNA circles can be unknotted, knotted or linked
(catenated). Such topological entanglements of DNA molecules
have important impact on biological processes.
Topoisomerases are a ubiquitous class of enzymes that pass
one DNA segment through another, serving critical biological
functions in cellular replication and maintenance of genome
stability. Experimentally, type-2 topoisomerases (topo II)
can reduce knot population by as much as 90 times and
catenane population by ~ 16 times. These observations raise
a fundamental question of physical principle: How does a
relatively small enzyme discern the global topology of a
much larger DNA molecule that it acts upon? Because it seems
that topo II can work magic, it has even been likened to
Maxwell's demon. This talk addresses the statistical
mechanical basis of topo II actions. Using coarse-grained
lattice and continuum wormlike chain models, we have
elucidated the mathematical basis of the hypothesis that
topo II recognize and act at specific DNA juxtapositions. We
found that selective segment passage at hooked geometries
can reduce knot populations as dramatically as seen in
experiments. Selective segment passage also provided
theoretical underpinning for an intriguing empirical scaling
relation between unknotting and decatenating potentials.
Such selective segment passage also accounts for supercoil
simplification (narrowing linking number distribution) by
topo II. The consistent agreement between theory and
experiment argues for topo II actions at hooked or
twisted-hooked DNA juxtapositions. Our investigation also
highlights a general connection between local geometry and
global topology in polymer configurations.
