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Pré-Publication, Document De Travail Année : 2020

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

Résumé

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.

Dates et versions

hal-03052966 , version 1 (10-12-2020)

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Olivier Hyrien, Diletta Ciardo, Olivier Haccard, Hemalatha Narassimprakash, Jean-Michel Arbona, et al.. Organization of DNA replication origin firing in Xenopus egg extracts : the role of intra-S checkpoint. 2020. ⟨hal-03052966⟩
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