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Enzyme Research
Volume 2011, Article ID 518258, 8 pages
Review Article

Trypanosome Prereplication Machinery: A Potential New Target for an Old Problem

Laboratório Especial de Toxinologia Aplicada (LETA) Center for Applied Toxinology (CAT/CEPID), Instituto Butantan, Avenida Vital Brasil 1500, 05503-000 São Paulo, SP, Brazil

Received 15 December 2010; Revised 16 March 2011; Accepted 30 March 2011

Academic Editor: Ariel M. Silber

Copyright © 2011 Simone Guedes Calderano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Approximately ten million people suffer from Chagas disease worldwide, caused by Trypanosoma cruzi, with the disease burden predominately focused in Latin America. Sleeping sickness is another serious health problem, caused by Trypanosoma brucei, especially in sub-Saharan countries. Unfortunately, the drugs currently available to treat these diseases have toxic effects and are not effective against all disease phases or parasite strains. Therefore, there is a clear need for the development of novel drugs and drug targets to treat these diseases. We propose the trypanosome prereplication machinery component, Orc1/Cdc6, as a potential target for drug development. In trypanosomes, Orc1/Cdc6 is involved in nuclear DNA replication, and, despite its involvement in such a conserved process, Orc1/Cdc6 is distinct from mammalian Orc1 and Cdc6 proteins. Moreover, RNAi-mediated silencing of trypanosome Orc1/Cdc6 expression in T. brucei decreased cell survival, indicating that Orc1/Cdc6 is critical for trypanosome survival.