2005 APS March Meeting
Monday–Friday, March 21–25, 2005;
Los Angeles, CA
Session A21: Focus Session: Dynamics of Transcription
8:00 AM–10:48 AM,
Monday, March 21, 2005
LACC
Room: 409A
Sponsoring
Unit:
DBP
Chair: Ken Dill, University of California-San Francisco
Abstract ID: BAPS.2005.MAR.A21.1
Abstract: A21.00001 : A double-ratchet mechanism of transcription elongation and its control*
8:00 AM–8:36 AM
Preview Abstract
Abstract
Author:
Andrei Ruckenstein
(Department of Physics and Astronomy and BioMaPS Institute for Quantitative Biology Rutgers University, Piscataway NJ 08854)
Transcription,
the process by which the genetic information encoded in DNA is
transferred
into RNA, is the first step in gene expression and it is the step
at which
most regulation occurs. A detailed understanding of the
structural and
mechanistic aspects of each step of transcription (initiation,
elongation,
termination and regulation) is one of the holy grails of biology.
Here we
characterize the motion of RNA polymerase (RNAP), the multi-subunit
molecular motor that carries out the transcription process,
during the
elongation stage. We argue that during elongation RNAP moves by a
complex
Brownian ratchet mechanism in which the translocation along DNA
and the
binding of nucleotides into RNAP's catalytic center are coupled to a
fluctuating internal degree of freedom associated with a protein
sub-unit
(the F-bridge) of RNAP. More precisely, the model is defined by a
set of
kinetic equations$^{ }$describing the competition for the
catalytic site
between an incoming nucleotide, the 3'-end of RNA, and the
F-bridge which in
its bent conformation blocks the active center. An important
aspect of the
model is the incorporation of the three ``active'' processes
describing (i)
the ejection of bound nucleotides from the active center through
steric
clashes with either the F-bridge in its bent conformation or with
the 3'-end
of RNA; and (ii) the forward translocation induced by bending of the
F-bridge pushing against the 3'-end of RNA. The ``active''
processes do not
imply a ``power stroke'' mechanism since the energy driving them
is purely
thermal. Indeed the model displays a route by which the system
uses thermal
fluctuations to control the rate, processivity and fidelity of
transcription
already before the irreversible chemical incorporation step.
Moreover, the
model qualitatively explains many aspects of both
bio-chemical\footnote{Bar-Nahum,
G., Epshtein, V., Ruckenstein, A.E., Rafikov, R., Mustaev, A.,
and Nudler,
E. A ratchet mechanism of transcription elongation and its
control. To
appear in Cell, 2005.} and
kinetic\footnote{Holmes, S.F., and Erie D.A.
Downstream DNA sequence effects on transcription elongation.
Allosteric
binding of nucleoside triphosphates facilitates translocation via
a ratchet
motion. J Biol Chem. $278$, 35597-35608.} experiments on
transcription elongation in \textit{E-coli} and makes a number
of falsifiable predictions.
*This work was done in collaboration with Daibhid O'Maoileidigh from the Department of Physics and the BioMaPS Institute at Rutgers and Evgeny Nudler's group from the Department of Biochemistry at the NYU Medical Center
To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2005.MAR.A21.1