Evolution of origin sequence and recognition for licensing of Eukaryotic DNA replication

In S. cerevisiae, origins are highly DNA sequence-specific and are recognized by the Origin Recognition Complex (ORC). In contrast, most eukaryotes have lost features in ORC subunits that contribute to DNA sequence-specific recognition, raising the question of how origins are identified.

An analysis of origins in the genome of the distantly related budding yeast Yarrowia lipolytica identified considerable variability in origin sequence and structure. High-resolution structures demonstrate that Y. lipolytica origins are recognized by a combination of ORC and Cdc6 in a manner different from S. cerevisiae. The structure of Yarrowia ORC-Cdc6 bound to different origins shows considerable plasticity in protein-DNA interactions.