DNA replication in yeast is stochastic

For many years, the temporal program governing DNA replication in budding yeast (S. cerevisiae) has been thought to be actively controlled by a deterministic timing mechanism. We present a reanalysis of microarray studies of DNA replication that supports an interpretation where stochastic effects play a key role and where timing is regulated indirectly by stochastic mechanisms, with no active control being required. Using a quantitative modeling approach, we show that it is possible for replication to be highly stochastic at the level of a single replication origin while simultaneously being highly reproducible at the level of population averages seen in microarray studies. We also discuss how one can extract useful information about replication origins from experiments performed on asynchronously replicating populations of cells, a result that opens up a much larger group of experiments to quantitative analysis.