Leishmania infantum EndoG Is an Endo/Exo-Nuclease Essential for Parasite Survival

EndoG, a member of the DNA/RNA non-specific ββα-metal family of nucleases, has been demonstrated to be present in many organisms, including Trypanosomatids. This nuclease participates in the apoptotic program in these parasites by migrating from the mitochondrion to the nucleus, where it takes part...

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Main Authors:	Rico, Eva, Oliva, Cristina, Gutierrez, Kilian Jesús, Alzate, Juan Fernando, Genes, Carlos Mario, Moreno, David, Casanova, Elena, Gigante, Alba, Pérez-Pérez, María-Jesús, Camarasa, María-José, Clos, Joachim, Gago, Federico, Jiménez-Ruiz, Antonio
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971528/

id	pubmed-3971528
recordtype	oai_dc
spelling	pubmed-39715282014-04-03 Leishmania infantum EndoG Is an Endo/Exo-Nuclease Essential for Parasite Survival Rico, Eva Oliva, Cristina Gutierrez, Kilian Jesús Alzate, Juan Fernando Genes, Carlos Mario Moreno, David Casanova, Elena Gigante, Alba Pérez-Pérez, María-Jesús Camarasa, María-José Clos, Joachim Gago, Federico Jiménez-Ruiz, Antonio Research Article EndoG, a member of the DNA/RNA non-specific ββα-metal family of nucleases, has been demonstrated to be present in many organisms, including Trypanosomatids. This nuclease participates in the apoptotic program in these parasites by migrating from the mitochondrion to the nucleus, where it takes part in the degradation of genomic DNA that characterizes this process. We now demonstrate that Leishmania infantum EndoG (LiEndoG) is an endo-exonuclease that has a preferential 5′ exonuclease activity on linear DNA. Regardless of its role during apoptotic cell death, this enzyme seems to be necessary during normal development of the parasites as indicated by the reduced growth rates observed in LiEndoG hemi-knockouts and their poor infectivity in differentiated THP-1 cells. The pro-life role of this protein is also corroborated by the higher survival rates of parasites that over-express this protein after treatment with the LiEndoG inhibitor Lei49. Taken together, our results demonstrate that this enzyme plays essential roles in both survival and death of Leishmania parasites. Public Library of Science 2014-02-26 /pmc/articles/PMC3971528/ /pubmed/24651293 http://dx.doi.org/10.1371/journal.pone.0089526 Text en © 2014 Rico 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rico, Eva Oliva, Cristina Gutierrez, Kilian Jesús Alzate, Juan Fernando Genes, Carlos Mario Moreno, David Casanova, Elena Gigante, Alba Pérez-Pérez, María-Jesús Camarasa, María-José Clos, Joachim Gago, Federico Jiménez-Ruiz, Antonio
spellingShingle	Rico, Eva Oliva, Cristina Gutierrez, Kilian Jesús Alzate, Juan Fernando Genes, Carlos Mario Moreno, David Casanova, Elena Gigante, Alba Pérez-Pérez, María-Jesús Camarasa, María-José Clos, Joachim Gago, Federico Jiménez-Ruiz, Antonio Leishmania infantum EndoG Is an Endo/Exo-Nuclease Essential for Parasite Survival
author_facet	Rico, Eva Oliva, Cristina Gutierrez, Kilian Jesús Alzate, Juan Fernando Genes, Carlos Mario Moreno, David Casanova, Elena Gigante, Alba Pérez-Pérez, María-Jesús Camarasa, María-José Clos, Joachim Gago, Federico Jiménez-Ruiz, Antonio
author_sort	Rico, Eva
title	Leishmania infantum EndoG Is an Endo/Exo-Nuclease Essential for Parasite Survival
title_short	Leishmania infantum EndoG Is an Endo/Exo-Nuclease Essential for Parasite Survival
title_full	Leishmania infantum EndoG Is an Endo/Exo-Nuclease Essential for Parasite Survival
title_fullStr	Leishmania infantum EndoG Is an Endo/Exo-Nuclease Essential for Parasite Survival
title_full_unstemmed	Leishmania infantum EndoG Is an Endo/Exo-Nuclease Essential for Parasite Survival
title_sort	leishmania infantum endog is an endo/exo-nuclease essential for parasite survival
description	EndoG, a member of the DNA/RNA non-specific ββα-metal family of nucleases, has been demonstrated to be present in many organisms, including Trypanosomatids. This nuclease participates in the apoptotic program in these parasites by migrating from the mitochondrion to the nucleus, where it takes part in the degradation of genomic DNA that characterizes this process. We now demonstrate that Leishmania infantum EndoG (LiEndoG) is an endo-exonuclease that has a preferential 5′ exonuclease activity on linear DNA. Regardless of its role during apoptotic cell death, this enzyme seems to be necessary during normal development of the parasites as indicated by the reduced growth rates observed in LiEndoG hemi-knockouts and their poor infectivity in differentiated THP-1 cells. The pro-life role of this protein is also corroborated by the higher survival rates of parasites that over-express this protein after treatment with the LiEndoG inhibitor Lei49. Taken together, our results demonstrate that this enzyme plays essential roles in both survival and death of Leishmania parasites.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971528/
_version_	1612072868395352064

Leishmania infantum EndoG Is an Endo/Exo-Nuclease Essential for Parasite Survival

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