Understanding the DNA replication programmes of the African trypanosome and Leishmania

Propagation of life requires genome replication. In eukaryotic cells, genome replication is a carefully controlled process involving a DNA replication programme dictated by defined sites, termed origins, where DNA replication initiates. However, cellular DNA replication programmes vary, including during development, and DNA replication can occur in the absence of origins and the factors they recruit. Understanding how cells balance origin-directed DNA replication programmes with more flexible, potentially back-up reactions has implications for genome evolution, for how organisms respond to changing environments, and for diseases that emerge from DNA replication perturbation. We seek to define the DNA replication programmes of two important single-celled eukaryotic parasites, Trypanosoma brucei and Leishmania major, where the balance of origin-directed DNA replication and potentially more flexible, poorly understood reactions appears unusual. By dissecting DNA replication programming, we will reveal how the parasites survive in mammals and how they adapt their growth and behaviour during transmission.