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

摘要

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 theta fromL. infantum (LiPol theta), 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 LiPol theta were significantly more resistant to oxidative and interstrand cross-linking agents, e.g. hydrogen peroxide, cisplatin and mitomycin C. Moreover, LiPol theta-overexpressing parasites showed an increased infectivity toward its natural macrophage host. Therefore, we propose that LiPol theta is a translesion synthesis polymerase involved in parasite DNA damage tolerance, to confer resistance against macrophage aggression.