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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-49461

Engels, K; Giannattasio, M; Muzi-Falconi, M; Lopes, M; Ferrari, S (2011). 14-3-3 proteins regulate exonuclease 1-dependent processing of stalled replication forks. PLoS Genetics, 7(4):e1001367.

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Abstract

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.

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12 citations in Web of Science®
11 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2011
Deposited On:09 Sep 2011 13:30
Last Modified:12 Nov 2014 12:24
Publisher:Public Library of Science (PLoS)
ISSN:1553-7390
Publisher DOI:10.1371/journal.pgen.1001367
PubMed ID:21533173

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