title: Nuclear DNA replication and repair in parasites of the genus Leishmania: Exploiting differences to develop innovative therapeutic approaches.
abstract: Leishmaniasis is a common tropical disease that affects mainly poor people in underdeveloped and developing countries. This largely neglected infection is caused by Leishmania spp, a parasite from the Trypanosomatidae family. This parasitic disease has different clinical manifestations, ranging from localized cutaneous to more harmful visceral forms. The main limitations of the current treatments are their high cost, toxicity, lack of specificity, and long duration. Efforts to improve treatments are necessary to deal with this infectious disease. Many approved drugs to combat diseases as diverse as cancer, bacterial, or viral infections take advantage of specific features of the causing agent or of the disease. Recent evidence indicates that the specific characteristics of the Trypanosomatidae replication and repair machineries could be used as possible targets for the development of new treatments. Here, we review in detail the molecular mechanisms of DNA replication and repair regulation in trypanosomatids of the genus Leishmania and the drugs that could be useful against this disease.
authors.affiliation: a Centro Internacional de Zoonosis, Facultad de Ciencias Químicas, Facultad de Medicina Veterinaria , Universidad Central del Ecuador , Quito , Ecuador.|b Programa Prometeo , SENESCYT, Whymper E7-37 y Alpallana, Quito , Ecuador.|c Facultad de Ciencias Naturales y Ambientales, Universidad Internacional SEK Calle Alberto Einstein sn y 5ta transversal , Quito , Ecuador.|d Fundación Instituto de Estudios Avanzados-IDEA , Caracas , Venezuela.
authors.forename: Graciela
authors.initials: G
authors.lastname: Uzcanga
authors.affiliation: a Centro Internacional de Zoonosis, Facultad de Ciencias Químicas, Facultad de Medicina Veterinaria , Universidad Central del Ecuador , Quito , Ecuador.|e Institute of Human Genetics , CNRS UPR 1142, 141 rue de la Cardonille, Equipe Labellisée Ligue Contre le Cancer , Montpellier cedex 5 , France.
authors.forename: Eliana
authors.initials: E
authors.lastname: Lara
authors.affiliation: a Centro Internacional de Zoonosis, Facultad de Ciencias Químicas, Facultad de Medicina Veterinaria , Universidad Central del Ecuador , Quito , Ecuador.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Gutiérrez
authors.affiliation: a Centro Internacional de Zoonosis, Facultad de Ciencias Químicas, Facultad de Medicina Veterinaria , Universidad Central del Ecuador , Quito , Ecuador.
authors.forename: Doyle
authors.initials: D
authors.lastname: Beaty
authors.affiliation: a Centro Internacional de Zoonosis, Facultad de Ciencias Químicas, Facultad de Medicina Veterinaria , Universidad Central del Ecuador , Quito , Ecuador.
authors.forename: Timo
authors.initials: T
authors.lastname: Beske
authors.affiliation: a Centro Internacional de Zoonosis, Facultad de Ciencias Químicas, Facultad de Medicina Veterinaria , Universidad Central del Ecuador , Quito , Ecuador.
authors.forename: Rommy
authors.initials: R
authors.lastname: Teran
authors.affiliation: a Centro Internacional de Zoonosis, Facultad de Ciencias Químicas, Facultad de Medicina Veterinaria , Universidad Central del Ecuador , Quito , Ecuador.|f Universidad Central de Venezuela, Instituto de Zoología y Ecología Tropical , Caracas , Venezuela.|g Facultad de Ciencias Naturales y Ambientales, Universidad Internacional SEK, Calle Alberto Einstein sn y 5ta transversal , Quito , Ecuador.
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Navarro
authors.affiliation: e Institute of Human Genetics , CNRS UPR 1142, 141 rue de la Cardonille, Equipe Labellisée Ligue Contre le Cancer , Montpellier cedex 5 , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pasero
authors.affiliation: a Centro Internacional de Zoonosis, Facultad de Ciencias Químicas, Facultad de Medicina Veterinaria , Universidad Central del Ecuador , Quito , Ecuador.
authors.forename: Washington
authors.initials: W
authors.lastname: Benítez
authors.affiliation: a Centro Internacional de Zoonosis, Facultad de Ciencias Químicas, Facultad de Medicina Veterinaria , Universidad Central del Ecuador , Quito , Ecuador.
authors.forename: Ana
authors.initials: A
authors.lastname: Poveda
mesh_terms: D000981:Antiprotozoal Agents / Q000302:isolation & purification* / Q000494:pharmacology; D004260:DNA Repair; D004261:DNA Replication; D055808:Drug Discovery; D007891:Leishmania / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007896:Leishmaniasis / Q000188:drug therapy*
chemical_list: D000981:Antiprotozoal Agents
keywords: DNA damage; DNA replication; Leishmania; drugs; genome stability