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Organization of DNA Replication Origin Firing in Xenopus 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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394201/ https://www.ncbi.nlm.nih.gov/pubmed/34440398 http://dx.doi.org/10.3390/genes12081224 |
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author | Ciardo, Diletta Haccard, Olivier Narassimprakash, Hemalatha Arbona, Jean-Michel Hyrien, Olivier Audit, Benjamin Marheineke, Kathrin Goldar, Arach |
author_facet | Ciardo, Diletta Haccard, Olivier Narassimprakash, Hemalatha Arbona, Jean-Michel Hyrien, Olivier Audit, Benjamin Marheineke, Kathrin Goldar, Arach |
author_sort | Ciardo, Diletta |
collection | PubMed |
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 Xenopus 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. |
format | Online Article Text |
id | pubmed-8394201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83942012021-08-28 Organization of DNA Replication Origin Firing in Xenopus Egg Extracts: The Role of Intra-S Checkpoint Ciardo, Diletta Haccard, Olivier Narassimprakash, Hemalatha Arbona, Jean-Michel Hyrien, Olivier Audit, Benjamin Marheineke, Kathrin Goldar, Arach Genes (Basel) Article 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 Xenopus 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. MDPI 2021-08-09 /pmc/articles/PMC8394201/ /pubmed/34440398 http://dx.doi.org/10.3390/genes12081224 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ciardo, Diletta Haccard, Olivier Narassimprakash, Hemalatha Arbona, Jean-Michel Hyrien, Olivier Audit, Benjamin Marheineke, Kathrin Goldar, Arach Organization of DNA Replication Origin Firing in Xenopus Egg Extracts: The Role of Intra-S Checkpoint |
title | Organization of DNA Replication Origin Firing in Xenopus Egg Extracts: The Role of Intra-S Checkpoint |
title_full | Organization of DNA Replication Origin Firing in Xenopus Egg Extracts: The Role of Intra-S Checkpoint |
title_fullStr | Organization of DNA Replication Origin Firing in Xenopus Egg Extracts: The Role of Intra-S Checkpoint |
title_full_unstemmed | Organization of DNA Replication Origin Firing in Xenopus Egg Extracts: The Role of Intra-S Checkpoint |
title_short | Organization of DNA Replication Origin Firing in Xenopus Egg Extracts: The Role of Intra-S Checkpoint |
title_sort | organization of dna replication origin firing in xenopus egg extracts: the role of intra-s checkpoint |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394201/ https://www.ncbi.nlm.nih.gov/pubmed/34440398 http://dx.doi.org/10.3390/genes12081224 |
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