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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / enzymology
  • DNA Damage*
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / metabolism*
  • Leishmania infantum / cytology
  • Leishmania infantum / drug effects
  • Leishmania infantum / enzymology*
  • Leishmania infantum / genetics
  • Mice
  • Mutagens / toxicity
  • Oxidative Stress
  • RAW 264.7 Cells

Substances

  • Mutagens
  • DNA polymerase theta
  • DNA-Directed DNA Polymerase