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...
Autores principales: | , , |
---|---|
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 |