The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo.

In budding yeast, the Pif1 DNA helicase is involved in the maintenance of both nuclear and mitochondrial genomes, but its role in these processes is still poorly understood. Here, we provide evidence for a new Pif1 function by demonstrating that its absence promotes genetic instability of alleles of...

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Main Authors: Cyril Ribeyre, Judith Lopes, Jean-Baptiste Boulé, Aurèle Piazza, Aurore Guédin, Virginia A Zakian, Jean-Louis Mergny, Alain Nicolas
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-05-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC2673046?pdf=render
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author Cyril Ribeyre
Judith Lopes
Jean-Baptiste Boulé
Aurèle Piazza
Aurore Guédin
Virginia A Zakian
Jean-Louis Mergny
Alain Nicolas
author_facet Cyril Ribeyre
Judith Lopes
Jean-Baptiste Boulé
Aurèle Piazza
Aurore Guédin
Virginia A Zakian
Jean-Louis Mergny
Alain Nicolas
author_sort Cyril Ribeyre
collection DOAJ
description In budding yeast, the Pif1 DNA helicase is involved in the maintenance of both nuclear and mitochondrial genomes, but its role in these processes is still poorly understood. Here, we provide evidence for a new Pif1 function by demonstrating that its absence promotes genetic instability of alleles of the G-rich human minisatellite CEB1 inserted in the Saccharomyces cerevisiae genome, but not of other tandem repeats. Inactivation of other DNA helicases, including Sgs1, had no effect on CEB1 stability. In vitro, we show that CEB1 repeats formed stable G-quadruplex (G4) secondary structures and the Pif1 protein unwinds these structures more efficiently than regular B-DNA. Finally, synthetic CEB1 arrays in which we mutated the potential G4-forming sequences were no longer destabilized in pif1Delta cells. Hence, we conclude that CEB1 instability in pif1Delta cells depends on the potential to form G-quadruplex structures, suggesting that Pif1 could play a role in the metabolism of G4-forming sequences.
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spelling doaj.art-311d01a8023949169b5d23b60453e1d22022-12-21T18:02:28ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042009-05-0155e100047510.1371/journal.pgen.1000475The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo.Cyril RibeyreJudith LopesJean-Baptiste BouléAurèle PiazzaAurore GuédinVirginia A ZakianJean-Louis MergnyAlain NicolasIn budding yeast, the Pif1 DNA helicase is involved in the maintenance of both nuclear and mitochondrial genomes, but its role in these processes is still poorly understood. Here, we provide evidence for a new Pif1 function by demonstrating that its absence promotes genetic instability of alleles of the G-rich human minisatellite CEB1 inserted in the Saccharomyces cerevisiae genome, but not of other tandem repeats. Inactivation of other DNA helicases, including Sgs1, had no effect on CEB1 stability. In vitro, we show that CEB1 repeats formed stable G-quadruplex (G4) secondary structures and the Pif1 protein unwinds these structures more efficiently than regular B-DNA. Finally, synthetic CEB1 arrays in which we mutated the potential G4-forming sequences were no longer destabilized in pif1Delta cells. Hence, we conclude that CEB1 instability in pif1Delta cells depends on the potential to form G-quadruplex structures, suggesting that Pif1 could play a role in the metabolism of G4-forming sequences.http://europepmc.org/articles/PMC2673046?pdf=render
spellingShingle Cyril Ribeyre
Judith Lopes
Jean-Baptiste Boulé
Aurèle Piazza
Aurore Guédin
Virginia A Zakian
Jean-Louis Mergny
Alain Nicolas
The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo.
PLoS Genetics
title The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo.
title_full The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo.
title_fullStr The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo.
title_full_unstemmed The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo.
title_short The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo.
title_sort yeast pif1 helicase prevents genomic instability caused by g quadruplex forming ceb1 sequences in vivo
url http://europepmc.org/articles/PMC2673046?pdf=render
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