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Nucleic Acids Res. 2016 Jun 2;44(10):4855-70. doi: 10.1093/nar/gkw346. Epub 2016 Apr 29.

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

Author information

1
Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain.
2
Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), 28049 Madrid, Spain.
3
Instituto de Parasitología y Biomedicina López-Neyra (CSIC), 18100 Granada, Spain.
4
Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain vlarraga@cib.csic.es.

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.

PMID:
27131366
PMCID:
PMC4889957
DOI:
10.1093/nar/gkw346
[Indexed for MEDLINE]
Free PMC Article

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