The yeast pif1 helicase prevents genomic instability caused by g-quadruplex-forming CEB1 sequences in vivo. Ribeyre, C., Lopes, J., Boulé, J., Piazza, A., Guédin, A., Zakian, V. a, Mergny, J., & Nicolas, A. PLoS Genetics, 5(5):e1000475, May, 2009. tex.ids= ribeyreYeastPif1Helicase2009
Paper doi abstract bibtex Changes in the primary DNA sequence are a major source of pathologies and cancers. The hereditary information also resides in secondary DNA structures, a layer of genetic information that remains poorly understood. Biophysical and structural studies have long established that, in vitro, the DNA molecule can adopt diverse structures different from the canonical Watson-Crick conformations. However, for a long time their existence in vivo has been regarded with a certain skepticism and their functional role elusive. One example is the G-quadruplex structure, which involves G-quartets that form between four DNA strands. Here, using in vitro and in vivo assays in the yeast S. cerevisiae, we reveal the unexpected role of the Pif1 helicase in maintaining the stability of the human CEB1 G-rich tandem repeat array. By site-directed mutagenesis, we show that the genomic instability of CEB1 repeats in absence of Pif1 and is directly dependent on the ability of CEB1 to form G-quadruplex structures. We show that Pif1 is very efficient in vitro in processing G-quadruplex structures formed by CEB1. We propose that Pif1 maintains CEB1 repeats by its ability to resolve G-quadruplex structures, thus providing circumstantial evidence of their formation in vivo.
@article{Ribeyre2009,
title = {The yeast pif1 helicase prevents genomic instability caused by g-quadruplex-forming {CEB1} sequences in vivo},
volume = {5},
issn = {1553-7404},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2673046&tool=pmcentrez&rendertype=abstract http://dx.doi.org/10.1371/journal.pgen.1000475 http://dx.plos.org/10.1371/journal.pgen.1000475},
doi = {10.1371/journal.pgen.1000475},
abstract = {Changes in the primary DNA sequence are a major source of pathologies and cancers. The hereditary information also resides in secondary DNA structures, a layer of genetic information that remains poorly understood. Biophysical and structural studies have long established that, in vitro, the DNA molecule can adopt diverse structures different from the canonical Watson-Crick conformations. However, for a long time their existence in vivo has been regarded with a certain skepticism and their functional role elusive. One example is the G-quadruplex structure, which involves G-quartets that form between four DNA strands. Here, using in vitro and in vivo assays in the yeast S. cerevisiae, we reveal the unexpected role of the Pif1 helicase in maintaining the stability of the human CEB1 G-rich tandem repeat array. By site-directed mutagenesis, we show that the genomic instability of CEB1 repeats in absence of Pif1 and is directly dependent on the ability of CEB1 to form G-quadruplex structures. We show that Pif1 is very efficient in vitro in processing G-quadruplex structures formed by CEB1. We propose that Pif1 maintains CEB1 repeats by its ability to resolve G-quadruplex structures, thus providing circumstantial evidence of their formation in vivo.},
number = {5},
journal = {PLoS Genetics},
author = {Ribeyre, Cyril and Lopes, Judith and Boulé, Jean-Baptiste and Piazza, Aurèle and Guédin, Aurore and Zakian, Virginia a and Mergny, Jean-Louis and Nicolas, Alain},
editor = {Cohen-Fix, Orna},
month = may,
year = {2009},
pmid = {19424434},
note = {tex.ids= ribeyreYeastPif1Helicase2009},
keywords = {Alleles, Base Composition, Base Sequence, DNA, DNA Helicases, DNA Helicases: metabolism, Fungal, Fungal: chemistry, Fungal: genetics, Fungal: metabolism, Genetic, Genomic Instability, Humans, Minisatellite Repeats, Models, Mutagenesis, Nucleic Acid Conformation, Rad51 Recombinase, Rad51 Recombinase: metabolism, Rad52 DNA Repair and Recombination Protein, Rad52 DNA Repair and Recombination Protein: metabo, Recombinant, Recombinant: chemistry, Recombinant: genetics, Recombinant: metabolism, Recombination, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Saccharomyces cerevisiae Proteins: metabolism, Saccharomyces cerevisiae: enzymology, Saccharomyces cerevisiae: genetics, Saccharomyces cerevisiae: growth \& development, Site-Directed},
pages = {e1000475},
}
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