Nuclear DNA replication initiation in kinetoplastid parasites: new insights into an ancient process

•Recent work has revealed new understanding of kinetoplastid nuclear DNA replication.•Putative kinetoplastid replication origin-binding factors are evolutionarily diverged.•Trypanosoma brucei nuclear DNA replication coordination conforms to some eukaryote paradigms.

Nuclear DNA replication is, arguably, the central cellular process in eukaryotes, because it drives propagation of life and intersects with many other genome reactions. Perhaps surprisingly, our understanding of nuclear DNA replication in kinetoplastids was limited until a clutch of studies emerged recently, revealing new insight into both the machinery and genome-wide coordination of the reaction. Here, we discuss how these studies suggest that the earliest acting components of the kinetoplastid nuclear DNA replication machinery – the factors that demarcate sites of the replication initiation, termed origins – are diverged from model eukaryotes. In addition, we discuss how origin usage and replication dynamics relate to the highly unusual organisation of transcription in the genome of Trypanosoma brucei.