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

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

Edité par CCSD -

During cell division, the duplication of the genome starts at multiple positions called 14 replication origins. Origin firing requires the interaction of rate-limiting factors with potential 15 origins during the S(ynthesis)-phase of the cell cycle. Origins fire as synchronous clusters is 16 proposed to be regulated by the intra-S checkpoint. By modelling either the unchallenged or the 17 checkpoint-inhibited replication pattern of single DNA molecules from Xenopus sperm chromatin 18 replicated in egg extracts, we demonstrate that the quantitative modelling of data require: 1) a 19 segmentation of the genome into regions of low and high probability of origin firing; 2) that regions 20 with high probability of origin firing escape intra-S checkpoint regulation; 3) that the intra-S 21 checkpoint controls the firing of replication origins in regions with low probability of firing. This 22 model implies that the intra-S checkpoint is not the main regulator of origin clustering. The minimal 23 nature of the proposed model foresees its use to analyse data from other eukaryotic organisms. 24 25

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