Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA-damage responses

CHANTAL REIGADA; MELISA SAYÉ; FABIO DI GIROLAMO; EDWARD A. VALERA VERA; CLAUDIO A. PEREIRA; MARIANA R. MIRANDA

MEMóRIAS DO INSTITUTO OSWALDO CRUZ.

FUNDACO OSWALDO CRUZ

Lugar: Rio de Janeiro; Año: 2020

0074-0276

BACKGROUND:NME23/NDPK proteins are well conserved proteins found in all living organisms. In addition to being nucleoside diphosphate kinases (NDPK),NDPKs are multifunctional enzymes involved in different processes such as DNA stability, gene regulation and DNA-repair among others. TcNDPK1 is the canonical NDPK isoform present in Trypanosoma cruzi, which has nuclease activity and DNA-binding properties in vitro. OBJECTIVES: In the present study we explored the role of TcNDPK1 in DNA-damage responses.METHODS: TcNDPK1 was expressed in mutant bacteria and yeasts and over-expressed in epimastigotes. Mutation frequencies, tolerance to genotoxic agents and activity of DNA-repair enzymes were evaluated.FINDINGS: Bacteria decreased about 15 fold the spontaneous mutation rate and yeasts were more resistant to hydrogen peroxide and to UV radiation than controls. Parasites over-expressing TcNDPK1 were able to withstand genotoxic stresses caused by hydrogen peroxide, phleomycin and hidroxyurea, presented lesser genomic damage and augmented levels of poly(ADP)ribose andpoly(ADP)ribose polymerase, an enzyme involved in DNA repair. MAIN CONCLUSION: These results strongly suggest that TcNDPK1 is involved in the maintenance of parasite?s genome integrity, thus, giving rise to a novel function.