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GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome

Previous studies have led to a picture wherein the replication of DNA progresses at variable rates over different parts of the budding yeast genome. These prior experiments, focused on production of nascent DNA, have been interpreted to imply that the dynamics of replication fork progression are str...

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Autores principales: Sekedat, Matthew D, Fenyö, David, Rogers, Richard S, Tackett, Alan J, Aitchison, John D, Chait, Brian T
Formato: Texto
Lenguaje:English
Publicado: European Molecular Biology Organization 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858444/
https://www.ncbi.nlm.nih.gov/pubmed/20212525
http://dx.doi.org/10.1038/msb.2010.8
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author Sekedat, Matthew D
Fenyö, David
Rogers, Richard S
Tackett, Alan J
Aitchison, John D
Chait, Brian T
author_facet Sekedat, Matthew D
Fenyö, David
Rogers, Richard S
Tackett, Alan J
Aitchison, John D
Chait, Brian T
author_sort Sekedat, Matthew D
collection PubMed
description Previous studies have led to a picture wherein the replication of DNA progresses at variable rates over different parts of the budding yeast genome. These prior experiments, focused on production of nascent DNA, have been interpreted to imply that the dynamics of replication fork progression are strongly affected by local chromatin structure/architecture, and by interaction with machineries controlling transcription, repair and epigenetic maintenance. Here, we adopted a complementary approach for assaying replication dynamics using whole genome time-resolved chromatin immunoprecipitation combined with microarray analysis of the GINS complex, an integral member of the replication fork. Surprisingly, our data show that this complex progresses at highly uniform rates regardless of genomic location, revealing that replication fork dynamics in yeast is simpler and more uniform than previously envisaged. In addition, we show how the synergistic use of experiment and modeling leads to novel biological insights. In particular, a parsimonious model allowed us to accurately simulate fork movement throughout the genome and also revealed a subtle phenomenon, which we interpret as arising from low-frequency fork arrest.
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spelling pubmed-28584442010-04-22 GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome Sekedat, Matthew D Fenyö, David Rogers, Richard S Tackett, Alan J Aitchison, John D Chait, Brian T Mol Syst Biol Article Previous studies have led to a picture wherein the replication of DNA progresses at variable rates over different parts of the budding yeast genome. These prior experiments, focused on production of nascent DNA, have been interpreted to imply that the dynamics of replication fork progression are strongly affected by local chromatin structure/architecture, and by interaction with machineries controlling transcription, repair and epigenetic maintenance. Here, we adopted a complementary approach for assaying replication dynamics using whole genome time-resolved chromatin immunoprecipitation combined with microarray analysis of the GINS complex, an integral member of the replication fork. Surprisingly, our data show that this complex progresses at highly uniform rates regardless of genomic location, revealing that replication fork dynamics in yeast is simpler and more uniform than previously envisaged. In addition, we show how the synergistic use of experiment and modeling leads to novel biological insights. In particular, a parsimonious model allowed us to accurately simulate fork movement throughout the genome and also revealed a subtle phenomenon, which we interpret as arising from low-frequency fork arrest. European Molecular Biology Organization 2010-03-09 /pmc/articles/PMC2858444/ /pubmed/20212525 http://dx.doi.org/10.1038/msb.2010.8 Text en Copyright © 2010, EMBO and Macmillan Publishers Limited https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution and reproduction in any medium, provided the original author and source are credited. Creation of derivative works is permitted but the resulting work may be distributed only under the same or similar licence to this one. This licence does not permit commercial exploitation without specific permission.
spellingShingle Article
Sekedat, Matthew D
Fenyö, David
Rogers, Richard S
Tackett, Alan J
Aitchison, John D
Chait, Brian T
GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome
title GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome
title_full GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome
title_fullStr GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome
title_full_unstemmed GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome
title_short GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome
title_sort gins motion reveals replication fork progression is remarkably uniform throughout the yeast genome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858444/
https://www.ncbi.nlm.nih.gov/pubmed/20212525
http://dx.doi.org/10.1038/msb.2010.8
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