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14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks
Replication fork integrity, which is essential for the maintenance of genome stability, is monitored by checkpoint-mediated phosphorylation events. 14-3-3 proteins are able to bind phosphorylated proteins and were shown to play an undefined role under DNA replication stress. Exonuclease 1 (Exo1) pro...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077382/ https://www.ncbi.nlm.nih.gov/pubmed/21533173 http://dx.doi.org/10.1371/journal.pgen.1001367 |
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author | Engels, Kim Giannattasio, Michele Muzi-Falconi, Marco Lopes, Massimo Ferrari, Stefano |
author_facet | Engels, Kim Giannattasio, Michele Muzi-Falconi, Marco Lopes, Massimo Ferrari, Stefano |
author_sort | Engels, Kim |
collection | PubMed |
description | Replication fork integrity, which is essential for the maintenance of genome stability, is monitored by checkpoint-mediated phosphorylation events. 14-3-3 proteins are able to bind phosphorylated proteins and were shown to play an undefined role under DNA replication stress. Exonuclease 1 (Exo1) processes stalled replication forks in checkpoint-defective yeast cells. We now identify 14-3-3 proteins as in vivo interaction partners of Exo1, both in yeast and mammalian cells. Yeast 14-3-3–deficient cells fail to induce Mec1–dependent Exo1 hyperphosphorylation and accumulate Exo1–dependent ssDNA gaps at stalled forks, as revealed by electron microscopy. This leads to persistent checkpoint activation and exacerbated recovery defects. Moreover, using DNA bi-dimensional electrophoresis, we show that 14-3-3 proteins promote fork progression under limiting nucleotide concentrations. We propose that 14-3-3 proteins assist in controlling the phosphorylation status of Exo1 and additional unknown targets, promoting fork progression, stability, and restart in response to DNA replication stress. |
format | Text |
id | pubmed-3077382 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30773822011-04-29 14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks Engels, Kim Giannattasio, Michele Muzi-Falconi, Marco Lopes, Massimo Ferrari, Stefano PLoS Genet Research Article Replication fork integrity, which is essential for the maintenance of genome stability, is monitored by checkpoint-mediated phosphorylation events. 14-3-3 proteins are able to bind phosphorylated proteins and were shown to play an undefined role under DNA replication stress. Exonuclease 1 (Exo1) processes stalled replication forks in checkpoint-defective yeast cells. We now identify 14-3-3 proteins as in vivo interaction partners of Exo1, both in yeast and mammalian cells. Yeast 14-3-3–deficient cells fail to induce Mec1–dependent Exo1 hyperphosphorylation and accumulate Exo1–dependent ssDNA gaps at stalled forks, as revealed by electron microscopy. This leads to persistent checkpoint activation and exacerbated recovery defects. Moreover, using DNA bi-dimensional electrophoresis, we show that 14-3-3 proteins promote fork progression under limiting nucleotide concentrations. We propose that 14-3-3 proteins assist in controlling the phosphorylation status of Exo1 and additional unknown targets, promoting fork progression, stability, and restart in response to DNA replication stress. Public Library of Science 2011-04-14 /pmc/articles/PMC3077382/ /pubmed/21533173 http://dx.doi.org/10.1371/journal.pgen.1001367 Text en Engels et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Engels, Kim Giannattasio, Michele Muzi-Falconi, Marco Lopes, Massimo Ferrari, Stefano 14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks |
title | 14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks |
title_full | 14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks |
title_fullStr | 14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks |
title_full_unstemmed | 14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks |
title_short | 14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks |
title_sort | 14-3-3 proteins regulate exonuclease 1–dependent processing of stalled replication forks |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077382/ https://www.ncbi.nlm.nih.gov/pubmed/21533173 http://dx.doi.org/10.1371/journal.pgen.1001367 |
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