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Replication origins and timing of temporal replication in budding yeast: How to solve the conundrum?

Barberis, Matteo, Spiesser, T.W. and Klipp, E. (2010) Replication origins and timing of temporal replication in budding yeast: How to solve the conundrum? Current Genomics, 11 (3). pp. 199-211.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Spiesser, T.W.
Klipp, E.
Date : 2010
DOI : 10.2174/138920210791110942
Uncontrolled Keywords : Budding yeast; Clb5; DNA replication; Genomic instability; Origins of replication; Sic1; Stochastic firing; Temporal program
Depositing User : Clive Harris
Date Deposited : 16 Apr 2019 09:54
Last Modified : 16 Apr 2019 09:54

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