arXiv subjects

Shubhadeep Patra

Publications and source records attributed to Shubhadeep Patra.

4 recordsLinked to original sources

arXiv2019

A Biologically Motivated Asymmetric Exclusion Process: interplay of congestion in RNA polymerase traffic and slippage of nascent transcript

We develope a theoretical framework, based on exclusion process, that is motivated by a biological phenomenon called transcript slippage (TS). In this model a discrete lattice represents a DNA strand while each of the particles that hop on it unidirectionally, from site to site, represents a RNA polymerase (RNAP). While walking like a molecular motor along a DNA track in a step-by-step manner, a RNAP simultaneously synthesizes a RNA chain; in each forward step it elongates the nascent RNA molecule by one unit, using the DNA track also as the template. At some special "slippery" position on the DNA, which we represent as a defect on the lattice, a RNAP can lose its grip on the nascent RNA and the latter's consequent slippage results in a final product that is either longer or shorter than the corresponding DNA template. We develope an exclusion model for RNAP traffic where the kinetics of the system at the defect site captures key features of TS events. We demonstrate the interplay of the crowding of RNAPs and TS. A RNAP has to wait at the defect site for longer period in a more congested RNAP traffic, thereby increasing the likelihood of its suffering a larger number of TS events. The qualitative trends of some of our results for a simple special case of our model are consistent with experimental observations. The general theoretical framework presented here will be useful for guiding future experimental queries and for analysis of the experimental data with more detailed versions of the same model.

cond-mat.stat-mech↗

arXiv2018

Molecular force spectroscopy of kinetochore-microtubule attachment {\it in silico}: Mechanical signatures of an unusual catch bond and collective effects

Measurement of the life time of attachments formed by a single microtubule (MT) with a single kinetochore (kt) {\it in-vitro} under force-clamp conditions had earlier revealed a catch-bond-like behavior. In the past the physical origin of this apparently counter-intuitive phenomenon was traced to the nature of the force-dependence of the (de-)polymerization kinetics of the MTs. Here first the same model MT-kt attachment is subjected to external tension that increases linearly with time until rupture occurs. In our {\it force-ramp} experiments {\it in-silico}, the model displays the well known `mechanical signatures' of a catch-bond probed by molecular force spectroscopy. Exploiting this new evidence, we have further strengthened the analogy between MT-kt attachments and common ligand-receptor bonds in spite of the crucial differences in their underlying physical mechanisms. We then extend the formalism to model the stochastic kinetics of an attachment formed by a bundle of multiple parallel microtubules with a single kt considering the effect of rebinding under force-clamp and force-ramp conditions. From numerical studies of the model we predict the trends of variation of the mean life time and mean rupture force with the increasing number of MTs in the bundle. Both the mean life time and the mean rupture force display nontrivial nonlinear dependence on the maximum number of MTs that can attach simultaneously to the same kt.

physics.bio-ph↗

arXiv2018

A biologically inspired two-species exclusion model: effects of RNA polymerase motor traffic on simultaneous DNA replication

We introduce a two-species exclusion model to describe the key features of the conflict between the RNA polymerase (RNAP) motor traffic, engaged in the transcription of a segment of DNA, concomitant with the progress of two DNA replication forks on the same DNA segment. One of the species of particles ($P$) represents RNAP motors while the other ($R$) represents replication forks. Motivated by the biological phenomena that this model is intended to capture, a maximum of only two $R$ particles are allowed to enter the lattice from two opposite ends whereas the unrestricted number of $P$ particles constitute a totally asymmetric simple exclusion process (TASEP) in a segment in the middle of the lattice. Consequently, the lattice consists of three segments; the encounters of the $P$ particles with the $R$ particles are confined within the middle segment (segment $2$) whereas only the $R$ particles can occupy the sites in the segments $1$ and $3$. The model captures three distinct pathways for resolving the co-directional as well as head-collision between the $P$ and $R$ particles. Using Monte Carlo simulations and heuristic analytical arguments that combine exact results for the TASEP with mean-field approximations, we predict the possible outcomes of the conflict between the traffic of RNAP motors ($P$ particles engaged in transcription) and the replication forks ($R$ particles). The outcomes, of course, depend on the dynamical phase of the TASEP of $P$ particles. In principle, the model can be adapted to the experimental conditions to account for the data quantitatively.

q-bio.SC↗

arXiv2017

First Passage Time in Computation by Tape-Copying Turing Machines: Slippage of Nascent Tape

Transcription of the genetic message encoded chemically in the sequence of the DNA template is carried out by a molecular machine called RNA polymerase (RNAP). Backward or forward slippage of the nascent RNA with respect to the DNA template strand give rise to a transcript that is, respectively, longer or shorter than the corresponding template. We model a RNAP as a "Tape-copying Turing machine" (TCTM) where the DNA template is the input tape while the nascent RNA strand is the output tape. Although the TCTM always steps forward the process is assumed to be stochastic that has a probability of occurrence per unit time. The time taken by a TCTM for each single successful forward stepping on the input tape, during which the output tape suffers lengthening or shortening by $n$ units because of backward or forward slippage, is a random variable; we report some of the statistical characteristics of this time by using the formalism for calculation of the distributions of {\it first-passage time}. The results are likely to find applications in the analysis of experimental data on "programmed" transcriptional error caused by transcriptional slippage which is a mode of "recoding" of genetic information.

physics.bio-ph↗