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Organization of DNA replication origin firing in Xenopus egg extracts : the role of intra-S checkpoint

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Hyrien, Olivier | Ciardo, Diletta | Haccard, Olivier | Narassimprakash, Hemalatha | Arbona, Jean-Michel | Audit, Benjamin | Marheineke, Kathrin | Goldar, Arach

Edité par CCSD -

During cell division, the duplication of the genome starts at multiple positions called replication origins. Origin firing requires the interaction of rate-limiting factors with potential origins during the S(ynthesis)-phase of the cell cycle. Origins fire as synchronous clusters is proposed to be regulated by the intra-S checkpoint. By modelling either the unchallenged or the checkpoint-inhibited replication pattern of single DNA molecules from Xenopus sperm chromatin replicated in egg extracts, we demonstrate that the quantitative modelling of data require: 1) a segmentation of the genome into regions of low and high probability of origin firing; 2) that regions with high probability of origin firing escape intra-S checkpoint regulation; 3) that the intra-S checkpoint controls the firing of replication origins in regions with low probability of firing. This model implies that the intra-S checkpoint is not the main regulator of origin clustering. The minimal nature of the proposed model foresees its use to analyse data from other eukaryotic organisms.

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