Unexpected role for Helicobacter pylori DNA polymerase I as a source of genetic variability.

Helicobacter pylori, a human pathogen infecting about half of the world population, is characterised by its large intraspecies variability. Its genome plasticity has been invoked as the basis for its high adaptation capacity. Consistent with its small genome, H. pylori possesses only two bona fide D...

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Autores principales:	María-Victoria García-Ortíz, Stéphanie Marsin, Mercedes E Arana, Didier Gasparutto, Raphaël Guérois, Thomas A Kunkel, J Pablo Radicella
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/5ec3512f6b754b0d8935bb17ddd4e756
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spelling	oai:doaj.org-article:5ec3512f6b754b0d8935bb17ddd4e7562021-11-18T06:17:18ZUnexpected role for Helicobacter pylori DNA polymerase I as a source of genetic variability.1553-73901553-740410.1371/journal.pgen.1002152https://doaj.org/article/5ec3512f6b754b0d8935bb17ddd4e7562011-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21731507/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Helicobacter pylori, a human pathogen infecting about half of the world population, is characterised by its large intraspecies variability. Its genome plasticity has been invoked as the basis for its high adaptation capacity. Consistent with its small genome, H. pylori possesses only two bona fide DNA polymerases, Pol I and the replicative Pol III, lacking homologues of translesion synthesis DNA polymerases. Bacterial DNA polymerases I are implicated both in normal DNA replication and in DNA repair. We report that H. pylori DNA Pol I 5'- 3' exonuclease domain is essential for viability, probably through its involvement in DNA replication. We show here that, despite the fact that it also plays crucial roles in DNA repair, Pol I contributes to genomic instability. Indeed, strains defective in the DNA polymerase activity of the protein, although sensitive to genotoxic agents, display reduced mutation frequencies. Conversely, overexpression of Pol I leads to a hypermutator phenotype. Although the purified protein displays an intrinsic fidelity during replication of undamaged DNA, it lacks a proofreading activity, allowing it to efficiently elongate mismatched primers and perform mutagenic translesion synthesis. In agreement with this finding, we show that the spontaneous mutator phenotype of a strain deficient in the removal of oxidised pyrimidines from the genome is in part dependent on the presence of an active DNA Pol I. This study provides evidence for an unexpected role of DNA polymerase I in generating genomic plasticity.María-Victoria García-OrtízStéphanie MarsinMercedes E AranaDidier GasparuttoRaphaël GuéroisThomas A KunkelJ Pablo RadicellaPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 7, Iss 6, p e1002152 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 María-Victoria García-Ortíz Stéphanie Marsin Mercedes E Arana Didier Gasparutto Raphaël Guérois Thomas A Kunkel J Pablo Radicella Unexpected role for Helicobacter pylori DNA polymerase I as a source of genetic variability.
description	Helicobacter pylori, a human pathogen infecting about half of the world population, is characterised by its large intraspecies variability. Its genome plasticity has been invoked as the basis for its high adaptation capacity. Consistent with its small genome, H. pylori possesses only two bona fide DNA polymerases, Pol I and the replicative Pol III, lacking homologues of translesion synthesis DNA polymerases. Bacterial DNA polymerases I are implicated both in normal DNA replication and in DNA repair. We report that H. pylori DNA Pol I 5'- 3' exonuclease domain is essential for viability, probably through its involvement in DNA replication. We show here that, despite the fact that it also plays crucial roles in DNA repair, Pol I contributes to genomic instability. Indeed, strains defective in the DNA polymerase activity of the protein, although sensitive to genotoxic agents, display reduced mutation frequencies. Conversely, overexpression of Pol I leads to a hypermutator phenotype. Although the purified protein displays an intrinsic fidelity during replication of undamaged DNA, it lacks a proofreading activity, allowing it to efficiently elongate mismatched primers and perform mutagenic translesion synthesis. In agreement with this finding, we show that the spontaneous mutator phenotype of a strain deficient in the removal of oxidised pyrimidines from the genome is in part dependent on the presence of an active DNA Pol I. This study provides evidence for an unexpected role of DNA polymerase I in generating genomic plasticity.
format	article
author	María-Victoria García-Ortíz Stéphanie Marsin Mercedes E Arana Didier Gasparutto Raphaël Guérois Thomas A Kunkel J Pablo Radicella
author_facet	María-Victoria García-Ortíz Stéphanie Marsin Mercedes E Arana Didier Gasparutto Raphaël Guérois Thomas A Kunkel J Pablo Radicella
author_sort	María-Victoria García-Ortíz
title	Unexpected role for Helicobacter pylori DNA polymerase I as a source of genetic variability.
title_short	Unexpected role for Helicobacter pylori DNA polymerase I as a source of genetic variability.
title_full	Unexpected role for Helicobacter pylori DNA polymerase I as a source of genetic variability.
title_fullStr	Unexpected role for Helicobacter pylori DNA polymerase I as a source of genetic variability.
title_full_unstemmed	Unexpected role for Helicobacter pylori DNA polymerase I as a source of genetic variability.
title_sort	unexpected role for helicobacter pylori dna polymerase i as a source of genetic variability.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/5ec3512f6b754b0d8935bb17ddd4e756
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Unexpected role for Helicobacter pylori DNA polymerase I as a source of genetic variability.

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