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Updated: Oct 31, 2025
In Vitro Drug Screening Against All Life Cycle Stages of Trypanosoma cruzi Using Parasites Expressing β-galactosidase
Published on: November 5, 2021
Bioinformatics and expression analysis of the Xeroderma Pigmentosum complementation group C (XPC) of Trypanosoma
K M Souza1, I C Mendes2, D M Dall'Igna1,3
1Universidade do Estado de Santa Catarina, Departamento de Produção Animal e Alimentos, Lages, SC, Brasil.
Abstract:
Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T.cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.
Insights
Xeroderma Pigmentosum complementation group C (XPC) protein is crucial for DNA repair. Introducing Trypanosoma evansi XPC into Trypanosoma cruzi impaired cell growth and DNA repair, highlighting the importance of functional XPC.
Area of Science:
- Molecular Biology
- Genetics
- Parasitology
Background:
- Nucleotide excision repair (NER) is a vital DNA repair pathway.
- Xeroderma Pigmentosum complementation group C (XPC) protein recognizes DNA damage for NER.
- XPC's role in DNA repair and other cellular processes is significant across organisms.
Purpose of the Study:
- Investigate the function and structural characteristics of XPC proteins in Trypanosoma cruzi and Trypanosoma evansi.
- Assess the impact of heterologous XPC expression on T. cruzi cellular processes.
- Understand the implications of XPC protein interactions in DNA repair.
Main Methods:
- 3D modeling of T. cruzi and T. evansi XPC proteins.
- Gene insertion of T. evansi XPC into T. cruzi.
- Comparative analysis of cell growth and division rates under normal and cisplatin-treated conditions.
Main Results:
- T. cruzi and T. evansi XPC proteins exhibit minimal structural differences.
- T. cruzi cells overexpressing T. evansi XPC showed slower growth and impaired DNA repair post-cisplatin treatment compared to those overexpressing native XPC.
- The heterologous TevXPC protein appears to interfere with endogenous TcXPC functions in T. cruzi.
Conclusions:
- Proper functioning of endogenous XPC is critical for T. cruzi cell viability and DNA repair.
- Exogenous XPC expression can negatively impact cellular processes due to altered protein interactions.
- This study underscores the specificity required for protein function within cellular pathways.
