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Title

A putative Leishmania DNA polymerase theta protects the parasite against oxidative damage

AuthorsFernández-Orgiler, Abel; Martínez-JimCrossed, María I.; Alonso, Ana ; Alcolea, Pedro J. ; Requena, José María ; Thomas, María del Carmen; Blanco, Luis ; Larraga, Vicente
Issue Date14-Apr-2016
PublisherOxford University Press
CitationNucleic Acids Research 44: 4855- 4870 (2016)
AbstractLeishmania 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.
URIhttp://hdl.handle.net/10261/150706
DOI10.1093/nar/gkw346
Identifiersdoi: 10.1093/nar/gkw346
issn: 1362-4962
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