BACKGROUND NME23/NDPKs are well conserved proteins found in all living organisms. In addition to being nucleoside diphosphate kinases (NDPK), they 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-folds the spontaneous mutation rate and yeasts were more resistant to hydrogen peroxide and to UV radiation than controls. Parasites overexpressing TcNDPK1 were able to withstand genotoxic stresses caused by hydrogen peroxide, phleomycin and hidroxyurea. They also presented less genomic damage and augmented levels of poly(ADP)ribose and poly(ADP)ribose polymerase, an enzyme involved in DNA repair. MAIN CONCLUSION These results strongly suggest a novel function for TcNDPK1; its involvement in the maintenance of parasite’s genome integrity.

中文翻译：

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克氏锥虫核苷二磷酸激酶 1 在 DNA 损伤反应中的作用。

背景 NME23/NDPKs 是在所有生物体中发现的高度保守的蛋白质。除了是核苷二磷酸激酶 (NDPK) 之外，它们还是参与不同过程的多功能酶，例如 DNA 稳定性、基因调控和 DNA 修复等。TcNDPK1 是存在于克氏锥虫中的典型 NDPK 同种型，在体外具有核酸酶活性和 DNA 结合特性。目的 在本研究中，我们探讨了 TcNDPK1 在 DNA 损伤反应中的作用。方法 TcNDPK1 在突变细菌和酵母中表达，并在上鞭毛体中过度表达。评估了突变频率、对基因毒剂的耐受性和 DNA 修复酶的活性。结果 与对照相比，细菌的自发突变率降低了约 15 倍，酵母对过氧化氢和紫外线辐射的抵抗力更强。过表达 TcNDPK1 的寄生虫能够承受由过氧化氢、腐草霉素和羟基脲引起的基因毒性压力。他们还表现出较少的基因组损伤和增加的聚（ADP）核糖和聚（ADP）核糖聚合酶水平，这是一种参与DNA修复的酶。主要结论 这些结果有力地表明了 TcNDPK1 的新功能。它参与维持寄生虫基因组的完整性。