title: A putative Leishmania DNA polymerase theta protects the parasite against oxidative damage.
abstract: Leishmania infantum is a protozoan parasite that is phagocytized by human macrophages. The host macrophages kill the parasite by generating oxidative compounds that induce DNA damage. We have identified, purified and biochemically characterized a DNA polymerase θ from L. infantum (LiPolθ), demonstrating that it is a DNA-dependent DNA polymerase involved in translesion synthesis of 8oxoG, abasic sites and thymine glycol lesions. Stably transfected L. infantum parasites expressing LiPolθ were significantly more resistant to oxidative and interstrand cross-linking agents, e.g. hydrogen peroxide, cisplatin and mitomycin C. Moreover, LiPolθ-overexpressing parasites showed an increased infectivity toward its natural macrophage host. Therefore, we propose that LiPolθ is a translesion synthesis polymerase involved in parasite DNA damage tolerance, to confer resistance against macrophage aggression.
authors.affiliation: Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain.
authors.forename: Abel
authors.initials: A
authors.lastname: Fernández-Orgiler
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: María I
authors.initials: MI
authors.lastname: Martínez-Jiménez
authors.affiliation: Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain.
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Alcolea
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Requena
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra (CSIC), 18100 Granada, Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: Thomas
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Blanco
authors.affiliation: Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain vlarraga@cib.csic.es.
authors.forename: Vicente
authors.initials: V
authors.lastname: Larraga
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism*; D018314:Leishmania infantum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D018384:Oxidative Stress; D000067996:RAW 264.7 Cells; D000097462:DNA Polymerase theta
chemical_list: D004259:DNA-Directed DNA Polymerase; D009153:Mutagens; D000097462:DNA Polymerase theta