The in vivo and in vitro roles of Trypanosoma cruzi Rad51 in the repair of DNA double strand breaks and oxidative lesions.

In Trypanosoma cruzi, the etiologic agent of Chagas disease, Rad51 (TcRad51) is a central enzyme for homologous recombination. Here we describe the different roles of TcRad51 in DNA repair. Epimastigotes of T. cruzi overexpressing TcRAD51 presented abundant TcRad51-labeled foci before gamma irradiation treatment, and a faster growth recovery when compared to single-knockout epimastigotes for RAD51. Overexpression of RAD51 also promoted increased resistance against hydrogen peroxide treatment, while the single-knockout epimastigotes for RAD51 exhibited increased sensitivity to this oxidant agent, which indicates a role for this gene in the repair of DNA oxidative lesions. In contrast, TcRad51 was not involved in the repair of crosslink lesions promoted by UV light and cisplatin treatment. Also, RAD51 single-knockout epimastigotes showed a similar growth rate to that exhibited by wild-type ones after treatment with hydroxyurea, but an increased sensitivity to methyl methane sulfonate. Besides its role in epimastigotes, TcRad51 is also important during mammalian infection, as shown by increased detection of T. cruzi cells overexpressing RAD51, and decreased detection of single-knockout cells for RAD51, in both fibroblasts and macrophages infected with amastigotes. Besides that, RAD51-overexpressing parasites infecting mice also presented increased infectivity and higher resistance against benznidazole. We thus show that TcRad51 is involved in the repair of DNA double strands breaks and oxidative lesions in two different T. cruzi developmental stages, possibly playing an important role in the infectivity of this parasite.

Toxic and Beneficial Potential of Silver Nanoparticles: The Two Sides of the Same Coin.

Nanotechnology has allowed great changes in chemical, biological and physical properties of metals when compared to their bulk counterparts. Within this context, silver nanoparticles (AgNPs) play a major role due to their unique properties, being widely used in daily products such as fabrics, washing machines, water filters, food and medicine. However, AgNPs can enter cells inducing a "Trojan-horse" type mechanism which potentially leads to cellular autophagy, apoptosis or necrosis. On the other hand, this cytotoxicity mechanism can be optimized to develop drug nanocarriers and anticancer therapies. The increasing use of these NPs entails their release into the environment, damaging ecosystems balance and representing a threat to human health. In this context, the possible deleterious effects that these NPs may represent for the biotic and abiotic ecosystems components represent an obstacle that must be overcome in order to guarantee the safety use of their unique properties.