Dutch led international team of researchers has unravelled
how nature releases the torque built up in DNA at
the molecular level. The researchers from Delft University
of Technology, the Ecole Normale Supérieure
in Paris and the Sloan-Kettering institute in New
York published their findings in the 31 March 2005
issue of Nature. An artistic impression of the enzyme
at work is featured on the cover of this issue.
The enzyme topoisomerase IB
releases the torsion built up in DNA strands. During
their investigations, the researchers could follow
a single topoisomerase-enzyme molecule over time as
it acted on a single DNA molecule. The topoisomerase
clamps onto the DNA, cuts through one of the two DNA
strands, and then lets the DNA unwind before sticking
the broken ends back together again. With the help
of sensitive measuring devices, the researchers could
measure various parameters such as the friction of
the rotating DNA in a cavity of the enzyme. The research
has provided new insights into the interactions between
DNA and the enzyme, which are of fundamental importance
for understanding cell division.
DNA consists of two long strands
joined together by pairs of bases. Both strands wind
around each other in the form of a double helix with
the base pairs acting as the 'stairs' in a staircase.
The sequence of these base pairs stores genetic information.
During cell division genetic material is copied and
the enzymes responsible for this must be able to transcribe
the base sequences. This is only possible if the portion
of DNA to be transcribed is unwound. This winding
and unwinding of the DNA gives rise to torsional forces
in the DNA, the magnitude of which increases as cell
division progresses. These forces can delay the process
of cell division and under certain conditions even
stop it. Topoisomerase IB can reduce these torsional
The enzyme releases the torsion
from the DNA as follows: The enzyme surrounds the
double-stranded DNA like a clamp and then temporarily
cuts through one of the two DNA strands. The accumulated
torsional forces in the DNA are then spun out around
the intact strand. After a number of turns the topoisomerase
ones again firmly grabs the spinning DNA and 'glues'
(ligates) the broken stands neatly back together again.
The researchers were able to determine the exact number
of turns removed by the topisomerase between 'cutting'
The precise mechanism of topoisomerase
IB is also important for cancer research. Drugs which
inhibit the functioning of topoisomerase IB are already
in clinical use, but can possibly be improved using
the knowledge from this study.
For further information please
Dr Nynke Dekker (Department
of Molecular Biophysics, Kavli Institute of NanoScience,
Delft University of Technology)
t: +31 (0)15 278 3219