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

Science. 2017 Jul 21;357(6348):314-318. doi: 10.1126/science.aan0063.


Bidirectional replication from eukaryotic DNA replication origins requires the loading of two ring-shaped minichromosome maintenance (MCM) helicases around DNA in opposite orientations. MCM loading is orchestrated by binding of the origin recognition complex (ORC) to DNA, but how ORC coordinates symmetrical MCM loading is unclear. We used natural budding yeast DNA replication origins and synthetic DNA sequences to show that efficient MCM loading requires binding of two ORC molecules to two ORC binding sites. The relative orientation of these sites, but not the distance between them, was found to be critical for MCM loading in vitro and origin function in vivo. We propose that quasi-symmetrical loading of individual MCM hexamers by ORC and directed MCM translocation into double hexamers acts as a unifying mechanism for the establishment of bidirectional replication in archaea and eukaryotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA Helicases / metabolism*
  • DNA Replication*
  • Minichromosome Maintenance Proteins / metabolism*
  • Origin Recognition Complex / metabolism*
  • Replication Origin
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*


  • Origin Recognition Complex
  • Saccharomyces cerevisiae Proteins
  • DNA Helicases
  • Minichromosome Maintenance Proteins