@article {Ciardo2020.06.22.164673, author = {Diletta Ciardo and Olivier Haccard and Hemalatha Narassimprakash and Jean-Michel Arbona and Olivier Hyrien and Benjamin Audit and Kathrin Marheineke and Arach Goldar}, title = {Organization of DNA replication origin firing in Xenopus egg extracts : the role of intra-S checkpoint}, elocation-id = {2020.06.22.164673}, year = {2020}, doi = {10.1101/2020.06.22.164673}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2020/06/23/2020.06.22.164673}, eprint = {https://www.biorxiv.org/content/early/2020/06/23/2020.06.22.164673.full.pdf}, journal = {bioRxiv} }