Organization of DNA Replication Origin Firing in <i>Xenopus</i> Egg Extracts: The Role of Intra-S Checkpoint
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 which is proposed t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/8/1224 |
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| author | Diletta Ciardo Olivier Haccard Hemalatha Narassimprakash Jean-Michel Arbona Olivier Hyrien Benjamin Audit Kathrin Marheineke Arach Goldar |
| author_facet | Diletta Ciardo Olivier Haccard Hemalatha Narassimprakash Jean-Michel Arbona Olivier Hyrien Benjamin Audit Kathrin Marheineke Arach Goldar |
| author_sort | Diletta Ciardo |
| collection | DOAJ |
| description | 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 which is proposed to be regulated by the intra-S checkpoint. By modelling the unchallenged, the checkpoint-inhibited and the checkpoint protein Chk1 over-expressed replication pattern of single DNA molecules from <i>Xenopus</i> sperm chromatin replicated in egg extracts, we demonstrate that the quantitative modelling of data requires: (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 and (3) the variability of the rate of DNA synthesis close to replication forks is a necessary ingredient that should be taken in to account in order to describe the dynamic of replication origin firing. This model implies that the observed origin clustering emerges from the apparent synchrony of origin firing in regions with high probability of origin firing and challenge the assumption that the intra-S checkpoint is the main regulator of origin clustering. |
| first_indexed | 2024-03-10T08:48:06Z |
| format | Article |
| id | doaj.art-c56f37e0fa6e4b1fb96959ef00e94a5b |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T08:48:06Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-c56f37e0fa6e4b1fb96959ef00e94a5b2023-11-22T07:46:19ZengMDPI AGGenes2073-44252021-08-01128122410.3390/genes12081224Organization of DNA Replication Origin Firing in <i>Xenopus</i> Egg Extracts: The Role of Intra-S CheckpointDiletta Ciardo0Olivier Haccard1Hemalatha Narassimprakash2Jean-Michel Arbona3Olivier Hyrien4Benjamin Audit5Kathrin Marheineke6Arach Goldar7Institute of Integrative Biology of the Cell (I2BC), CNRS, CEA, University Paris Sud, 1, Avenue de la Terrasse, 91190 Gif-sur-Yvette, FranceInstitute of Integrative Biology of the Cell (I2BC), CNRS, CEA, University Paris Sud, 1, Avenue de la Terrasse, 91190 Gif-sur-Yvette, FranceInstitute of Integrative Biology of the Cell (I2BC), CNRS, CEA, University Paris Sud, 1, Avenue de la Terrasse, 91190 Gif-sur-Yvette, FranceUniversity Lyon, ENS de Lyon, Laboratoire de Biologie et Modélisation de la Cellule, University Claude Bernard Lyon 1, CNRS UMR5239, INSERM U1210, 46 Allé d’Italie Site Jacques Monod, 69007 Lyon, FranceInstitut de Biologie de l’Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, FranceUniversity Lyon, ENS de Lyon, University Claude Bernard Lyon 1, CNRS, Laboratoire de Physique, 69342 Lyon, FranceInstitute of Integrative Biology of the Cell (I2BC), CNRS, CEA, University Paris Sud, 1, Avenue de la Terrasse, 91190 Gif-sur-Yvette, FranceInstitute of Integrative Biology of the Cell (I2BC), CNRS, CEA, University Paris Sud, 1, Avenue de la Terrasse, 91190 Gif-sur-Yvette, FranceDuring 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 which is proposed to be regulated by the intra-S checkpoint. By modelling the unchallenged, the checkpoint-inhibited and the checkpoint protein Chk1 over-expressed replication pattern of single DNA molecules from <i>Xenopus</i> sperm chromatin replicated in egg extracts, we demonstrate that the quantitative modelling of data requires: (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 and (3) the variability of the rate of DNA synthesis close to replication forks is a necessary ingredient that should be taken in to account in order to describe the dynamic of replication origin firing. This model implies that the observed origin clustering emerges from the apparent synchrony of origin firing in regions with high probability of origin firing and challenge the assumption that the intra-S checkpoint is the main regulator of origin clustering.https://www.mdpi.com/2073-4425/12/8/1224DNA replicationcheckpointmathematical modellingminimal modelorigin firing |
| spellingShingle | Diletta Ciardo Olivier Haccard Hemalatha Narassimprakash Jean-Michel Arbona Olivier Hyrien Benjamin Audit Kathrin Marheineke Arach Goldar Organization of DNA Replication Origin Firing in <i>Xenopus</i> Egg Extracts: The Role of Intra-S Checkpoint Genes DNA replication checkpoint mathematical modelling minimal model origin firing |
| title | Organization of DNA Replication Origin Firing in <i>Xenopus</i> Egg Extracts: The Role of Intra-S Checkpoint |
| title_full | Organization of DNA Replication Origin Firing in <i>Xenopus</i> Egg Extracts: The Role of Intra-S Checkpoint |
| title_fullStr | Organization of DNA Replication Origin Firing in <i>Xenopus</i> Egg Extracts: The Role of Intra-S Checkpoint |
| title_full_unstemmed | Organization of DNA Replication Origin Firing in <i>Xenopus</i> Egg Extracts: The Role of Intra-S Checkpoint |
| title_short | Organization of DNA Replication Origin Firing in <i>Xenopus</i> Egg Extracts: The Role of Intra-S Checkpoint |
| title_sort | organization of dna replication origin firing in i xenopus i egg extracts the role of intra s checkpoint |
| topic | DNA replication checkpoint mathematical modelling minimal model origin firing |
| url | https://www.mdpi.com/2073-4425/12/8/1224 |
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