Bidirectional eukaryotic DNA replication is established by quasi-symmetrical helicase loading

Abstract

Getting loaded—make mine a double! Chromosomal DNA replication initiates bidirectionally by loading two ring-shaped helicases onto DNA in opposite orientations. How this symmetry is achieved has been puzzling because replication initiation sites contain only one essential binding site for the initiator, the origin recognition complex (ORC). Coster and Diffley now show that both helicases are loaded by a similar mechanism. Efficient loading requires binding of two ORC complexes to two ORC binding sites in opposite orientations. Natural origins were found to be partially symmetrical, containing functionally relevant secondary ORC sites. Sites can be flexibly spaced, but introducing an intervening “roadblock” prevented loading, suggesting that individual helicases translocate toward each other on DNA to form a stable double ring. Science , this issue p. 314