Biomathematics Seminar: Fluctuations, backtracking and proofreading in DNA transcription
11 May 2010 14:15 in CM107
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 experiments
raise questions about the validity of such a simple single step picture.
I will present a multi-step model of transcription elongation
which demonstrates that transcription times are in general
non-Poisson distributed. In particular, the model takes account of transcriptional
pauses due to backtracking of the RNA polymerase. 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, the laws of thermodynamics imply necessarily that there are 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).