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On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway
DNA replication in eukaryotes is achieved by the activation of multiple replication origins which needs to be precisely coordinated in space and time. This spatio-temporal replication program is regulated by many factors to maintain genome stability, which is frequently threatened through stresses o...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410103/ https://www.ncbi.nlm.nih.gov/pubmed/30700024 http://dx.doi.org/10.3390/genes10020094 |
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author | Ciardo, Diletta Goldar, Arach Marheineke, Kathrin |
author_facet | Ciardo, Diletta Goldar, Arach Marheineke, Kathrin |
author_sort | Ciardo, Diletta |
collection | PubMed |
description | DNA replication in eukaryotes is achieved by the activation of multiple replication origins which needs to be precisely coordinated in space and time. This spatio-temporal replication program is regulated by many factors to maintain genome stability, which is frequently threatened through stresses of exogenous or endogenous origin. Intra-S phase checkpoints monitor the integrity of DNA synthesis and are activated when replication forks are stalled. Their activation leads to the stabilization of forks, to the delay of the replication program by the inhibition of late firing origins, and the delay of G2/M phase entry. In some cell cycles during early development these mechanisms are less efficient in order to allow rapid cell divisions. In this article, we will review our current knowledge of how the intra-S phase checkpoint regulates the replication program in budding yeast and metazoan models, including early embryos with rapid S phases. We sum up current models on how the checkpoint can inhibit origin firing in some genomic regions, but allow dormant origin activation in other regions. Finally, we discuss how numerical and theoretical models can be used to connect the multiple different actors into a global process and to extract general rules. |
format | Online Article Text |
id | pubmed-6410103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64101032019-03-26 On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway Ciardo, Diletta Goldar, Arach Marheineke, Kathrin Genes (Basel) Review DNA replication in eukaryotes is achieved by the activation of multiple replication origins which needs to be precisely coordinated in space and time. This spatio-temporal replication program is regulated by many factors to maintain genome stability, which is frequently threatened through stresses of exogenous or endogenous origin. Intra-S phase checkpoints monitor the integrity of DNA synthesis and are activated when replication forks are stalled. Their activation leads to the stabilization of forks, to the delay of the replication program by the inhibition of late firing origins, and the delay of G2/M phase entry. In some cell cycles during early development these mechanisms are less efficient in order to allow rapid cell divisions. In this article, we will review our current knowledge of how the intra-S phase checkpoint regulates the replication program in budding yeast and metazoan models, including early embryos with rapid S phases. We sum up current models on how the checkpoint can inhibit origin firing in some genomic regions, but allow dormant origin activation in other regions. Finally, we discuss how numerical and theoretical models can be used to connect the multiple different actors into a global process and to extract general rules. MDPI 2019-01-29 /pmc/articles/PMC6410103/ /pubmed/30700024 http://dx.doi.org/10.3390/genes10020094 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Ciardo, Diletta Goldar, Arach Marheineke, Kathrin On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway |
title | On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway |
title_full | On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway |
title_fullStr | On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway |
title_full_unstemmed | On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway |
title_short | On the Interplay of the DNA Replication Program and the Intra-S Phase Checkpoint Pathway |
title_sort | on the interplay of the dna replication program and the intra-s phase checkpoint pathway |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410103/ https://www.ncbi.nlm.nih.gov/pubmed/30700024 http://dx.doi.org/10.3390/genes10020094 |
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