Abstract Liverpool:

Genetic information is encoded in the nucleotide sequence of the DNA. This sequence contains the instruction code of the cell - determining protein structure and function, and hence cell function and fate.
Transcription is a vital stage in the process of gene expression and a major contributor to fluctuations in gene expression levels. It is typically modelled as a single step process with Poisson statistics. However, recent single molecule experiments raise questions about the validity of such a simple single step picture. I will present a molecular multi-step model of transcription elongation that demonstrates that transcription times are in general non-Poisson distributed. In particular, we model transcriptional pauses due to backtracking of the RNA polymerase as a first passage process. When transcriptional pauses result in long transcription times, I will demonstrate that this naturally leads to bursts of mRNA production and non-Poisson statistics of mRNA levels.
The viability and endurance of organisms crucially depend on the fidelity with which genetic information is transcribed/translated (during mRNA and protein production) and replicated (during DNA replication). However, thermodynamics introduces significant fluctuations which would incur large error rates if efficient proofreading mechanisms were not in place. I will examine a putative mechanism for error correction during DNA transcription, which relies on backtracking of the RNA polymerase (RNAP). This model will be used to calculate the error fraction as a function of the relevant rates (translocation, cleavage, backtracking and polymerization).