Emergence of replication timing patterns from stochastic origin firing

13 April 2012

Nicholas Rhind
Department of Biochemistry and Molecular Pharmacology
University of Massachusetts Medical School


Eukaryotic genomes replicate in define patterns with some origins in the genome firing early in S phase and others firing later. Replication timing correlates with transcription, chromatin modification, sub-nuclear localization and genome evolution, suggesting an intimate association between replication timing and other important aspects of chromosome metabolism. Based on an analytical model of genome-wide yeast replication kinetics, we propose that global replication timing is regulated by simple rules that effect the local probability of stochastic origin firing. Specifically, we propose that the probability of origin firing is governed by competition between origins for rate-limiting activators, and that the effectiveness with which origins compete is determined by an combination of the number of MCM complexes loaded at an origin (MCM being the replicative helicase and target of the activators) and the chromatin-regulated accessibly of MCM complexes to the activators. I will discuss the theoretical motivation for the model and our biochemical validation of it.

In collaboration with John Bechhoefer, Simon Fraser University

current theory lunch schedule