Nuclear DNA Replication in Trypanosomatids: There Are No Easy Methods for Solving Difficult Problems

In trypanosomatids, etiological agents of devastating diseases, replication is robust and finely controlled to maintain genome stability and function in stressful environments. However, these parasites encode several replication protein components and complexes that show potentially variant composition compared with model eukaryotes. This review focuses on the advances made in recent years regarding the differences and peculiarities of the replication machinery in trypanosomatids, including how such divergence might affect DNA replication dynamics and the replication stress response. Comparing the DNA replication machinery and processes of parasites and their hosts may provide a foundation for the identification of targets that can be used in the development of chemotherapies to assist in the eradication of diseases caused by these pathogens. In trypanosomatids, DNA replication is tightly controlled by protein complexes that diverge from those of model eukaryotes.There is no consensus for the number of replication origins used by trypanosomatids; how their replication dynamics compares with that of model organisms is the subject of debate.The DNA replication rate in trypanosomatids is similar to, but slightly higher than, that of model eukaryotes, which may be related to chromatin structure and function.Recent data suggest that the origin recognition complex in trypanosomatids closely resembles the multisubunit eukaryotic model.The absence of fundamental replication-associated proteins in trypanosomatids suggests that new signaling pathways may be present in these parasites to direct DNA replication and the replicative stress response.