title: Leishmania infantum EndoG is an endo/exo-nuclease essential for parasite survival.
abstract: 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.
authors.affiliation: Departamento de Biología de Sistemas-Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Rico
authors.affiliation: Departamento de Biología de Sistemas-Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Oliva
authors.affiliation: Departamento de Biología de Sistemas-Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: Kilian Jesús
authors.initials: KJ
authors.lastname: Gutierrez
authors.affiliation: Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Juan Fernando
authors.initials: JF
authors.lastname: Alzate
authors.affiliation: Departamento de Biología de Sistemas-Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: Carlos Mario
authors.initials: CM
authors.lastname: Genes
authors.affiliation: Departamento de Biología de Sistemas-Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Moreno
authors.affiliation: Instituto de Química Médica - Consejo Superior de Investigaciones Científicas (IQM-CSIC), Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Casanova
authors.affiliation: Instituto de Química Médica - Consejo Superior de Investigaciones Científicas (IQM-CSIC), Madrid, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Gigante
authors.affiliation: Instituto de Química Médica - Consejo Superior de Investigaciones Científicas (IQM-CSIC), Madrid, Spain.
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Pérez-Pérez
authors.affiliation: Instituto de Química Médica - Consejo Superior de Investigaciones Científicas (IQM-CSIC), Madrid, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Camarasa
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
authors.affiliation: Departamento de Ciencias Biomédicas - Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Alcalá de Henares, Madrid, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Gago
authors.affiliation: Departamento de Biología de Sistemas-Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jiménez-Ruiz
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism*; D018314:Leishmania infantum / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*
chemical_list: D004706:Endodeoxyribonucleases; D004720:Endonucleases; D005092:Exonucleases; C052391:endonuclease G; C020104:endoexonuclease