Functional dynamics of Orc1b protein: a ChIP-seq analysis

Abstract

Trypanosoma cruzi is a protozoan which belongs to the Trypanosomatidae family and it is the etiological agent of Chagas disease, a neglected disease that affects millions of people worldwide. This parasite alternates between replicative (epi and amastigotes) and non-replicative (trypomastigotes) forms in its hosts. Therefore, it needs intense control of DNA replication, which involves coordinated action of several proteins. DNA replication starts with the assembly of the pre-replication complex (pre-RC) component ORC onto replication origins, located near the nucleosomes. Followed by the recruitment of other proteins from pre-RC, including Orc1b, whose function is not yet clear. Preliminary data of Marques, et al. (2016) indicates Orc1b participation as a positive regulator in the replication instead of having only a structural role in the ORC complex and preliminary data from our group suggest the binding of Orc1b with the DNA. Thus, we aim to deepen the studies of the Orc1b role in the DNA replication of T. cruzi and its possible interactors. More specifically, this project aims to determine the DNA sequence bound by TcOrc1b by ChIP-seq in order to evaluate the role of this protein in the pre-RC, to be carried out at The Siegel lab in the Biomedical Center Munich (BMC), at the Ludwig-Maximilians-Universität, Munich, Germany. This knowledge will support the development of future antiparasitic strategies and it will also be useful to further understand the biology of these parasites.