Where it all starts: eukaryotic origins of DNA replication

Chromosomal origins of DNA replication in eukaryotic cells not only are cru cial for understanding the basic process of DNA duplication but also provid e a tool to analyze how cell cycle regulators are linked to the replication machinery. During the past decade much progress has been made in identifyi ng replication origins in eukaryotic genomes. More recently, replication in itiation point (RTP) mapping has allowed us to detect start sites for DNA s ynthesis at the nucleotide level and thus to monitor. replication initiatio n events at the origin very precisely. Beyond giving us the precise positio ns of start sites, the application of RIP mapping in yeast and human cells has revealed a single, defined start point at which replication initiates, a scenario very reminiscent of transcription initiation. More importantly, studies in yeast have shown that the binding site for the initiator, the or igin recognition complex (ORC), lies immediately adjacent to the replicatio n start point, which suggests that ORC directs the initiation machinery to a distinct site. Therefore, in our pursuit of identifying ORC-binding sites in higher eukaryotes, RIP mapping may lead the way.