Cargando…

Model-based analysis of DNA replication profiles: predicting replication fork velocity and initiation rate by profiling free-cycling cells

Eukaryotic cells initiate DNA synthesis by sequential firing of hundreds of origins. This ordered replication is described by replication profiles, which measure the DNA content within a cell population. Here, we show that replication dynamics can be deduced from replication profiles of free-cycling...

Descripción completa

Detalles Bibliográficos
Autores principales: Gispan, Ariel, Carmi, Miri, Barkai, Naama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287236/
https://www.ncbi.nlm.nih.gov/pubmed/28028072
http://dx.doi.org/10.1101/gr.205849.116
_version_ 1782504132810113024
author Gispan, Ariel
Carmi, Miri
Barkai, Naama
author_facet Gispan, Ariel
Carmi, Miri
Barkai, Naama
author_sort Gispan, Ariel
collection PubMed
description Eukaryotic cells initiate DNA synthesis by sequential firing of hundreds of origins. This ordered replication is described by replication profiles, which measure the DNA content within a cell population. Here, we show that replication dynamics can be deduced from replication profiles of free-cycling cells. While such profiles lack explicit temporal information, they are sensitive to fork velocity and initiation capacity through the passive replication pattern, namely the replication of origins by forks emanating elsewhere. We apply our model-based approach to a compendium of profiles that include most viable budding yeast mutants implicated in replication. Predicted changes in fork velocity or initiation capacity are verified by profiling synchronously replicating cells. Notably, most mutants implicated in late (or early) origin effects are explained by global modulation of fork velocity or initiation capacity. Our approach provides a rigorous framework for analyzing DNA replication profiles of free-cycling cells.
format Online
Article
Text
id pubmed-5287236
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-52872362017-08-01 Model-based analysis of DNA replication profiles: predicting replication fork velocity and initiation rate by profiling free-cycling cells Gispan, Ariel Carmi, Miri Barkai, Naama Genome Res Method Eukaryotic cells initiate DNA synthesis by sequential firing of hundreds of origins. This ordered replication is described by replication profiles, which measure the DNA content within a cell population. Here, we show that replication dynamics can be deduced from replication profiles of free-cycling cells. While such profiles lack explicit temporal information, they are sensitive to fork velocity and initiation capacity through the passive replication pattern, namely the replication of origins by forks emanating elsewhere. We apply our model-based approach to a compendium of profiles that include most viable budding yeast mutants implicated in replication. Predicted changes in fork velocity or initiation capacity are verified by profiling synchronously replicating cells. Notably, most mutants implicated in late (or early) origin effects are explained by global modulation of fork velocity or initiation capacity. Our approach provides a rigorous framework for analyzing DNA replication profiles of free-cycling cells. Cold Spring Harbor Laboratory Press 2017-02 /pmc/articles/PMC5287236/ /pubmed/28028072 http://dx.doi.org/10.1101/gr.205849.116 Text en © 2017 Gispan et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Method
Gispan, Ariel
Carmi, Miri
Barkai, Naama
Model-based analysis of DNA replication profiles: predicting replication fork velocity and initiation rate by profiling free-cycling cells
title Model-based analysis of DNA replication profiles: predicting replication fork velocity and initiation rate by profiling free-cycling cells
title_full Model-based analysis of DNA replication profiles: predicting replication fork velocity and initiation rate by profiling free-cycling cells
title_fullStr Model-based analysis of DNA replication profiles: predicting replication fork velocity and initiation rate by profiling free-cycling cells
title_full_unstemmed Model-based analysis of DNA replication profiles: predicting replication fork velocity and initiation rate by profiling free-cycling cells
title_short Model-based analysis of DNA replication profiles: predicting replication fork velocity and initiation rate by profiling free-cycling cells
title_sort model-based analysis of dna replication profiles: predicting replication fork velocity and initiation rate by profiling free-cycling cells
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287236/
https://www.ncbi.nlm.nih.gov/pubmed/28028072
http://dx.doi.org/10.1101/gr.205849.116
work_keys_str_mv AT gispanariel modelbasedanalysisofdnareplicationprofilespredictingreplicationforkvelocityandinitiationratebyprofilingfreecyclingcells
AT carmimiri modelbasedanalysisofdnareplicationprofilespredictingreplicationforkvelocityandinitiationratebyprofilingfreecyclingcells
AT barkainaama modelbasedanalysisofdnareplicationprofilespredictingreplicationforkvelocityandinitiationratebyprofilingfreecyclingcells