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DNA polymerase β of Leishmania donovani is important for infectivity and it protects the parasite against oxidative damage.
International Journal of Biological Macromolecules 2018 November 17
The visceral leishmaniasis is caused by L. donovani, a neglected tropical disease with an estimated number of 500,000 cases worldwide. Apart from the absence of effective vaccine, the available drugs have limitations like toxic side effects and emergence of drug resistance. The genome of Leishmania is remarkably challenged by the oxidative stress present inside the human macrophage. To maintain genomic integrity, a number of specialized DNA repair pathways assist in the recognition and repair of damaged DNA. In general, Base Excision Repair (BER) plays an essential role in the maintenance of genomic stability. We demonstrate here that the treatment of L. donovani with oxidative agents causes DNA damage and upregulation of Polβ. On the other hand, parasite overexpressing Polβ shows more resistance against Amp B, H2 O2 and menadione as compared to wild type cells. We also observed a higher infectivity in the parasites that overexpress Polβ. The upregulation of Polβ was also found in stationary phase and axenic amastigote of L. donovani. Overall, we propose that Polβ is crucial for infectivity and survival of the parasite. Discovery of specific inhibitors against Polβ could offer an attractive strategy against leishmaniasis.
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