Similarly to metazoans, the budding yeast Saccharomyces cereviasiae replicates
its genome with a defined timing. In this organism, well-defined, site-specific origins, are
efficient and fire in almost every round of DNA replication. However, this strategy is neither
conserved in the fission yeast Saccharomyces pombe, nor in Xenopus or Drosophila
embryos, nor in higher eukaryotes, in which DNA replication initiates asynchronously
throughout S phase at random sites. Temporal and spatial controls can contribute to the
timing of replication such as Cdk activity, origin localization, epigenetic status or gene
expression. However, a debate is going on to answer the question how individual origins are
selected to fire in budding yeast. Two opposing theories were proposed: the “replicon
paradigm” or “temporal program” vs. the “stochastic firing”. Recent data support the
temporal regulation of origin activation, clustering origins into temporal blocks of early and
late replication. Contrarily, strong evidences suggest that stochastic processes acting on
origins can generate the observed kinetics of replication without requiring a temporal order.
In mammalian cells, a spatiotemporal model that accounts for a partially deterministic and
partially stochastic order of DNA replication has been proposed. Is this strategy the solution
to reconcile the conundrum of having both organized replication timing and stochastic origin
firing also for budding yeast? In this review we discuss this possibility in the light of our
recent study on the origin activation, suggesting that there might be a stochastic component
in the temporal activation of the replication origins, especially under perturbed conditions.
Keywords: Budding yeast, DNA replication, origins of replication, temporal
program, stochastic firing, genomic instability, Clb5, Sic1.
