Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy

Jingchuan Sun, Hironori Kawakami, Juergen Zech, Christian Speck, Bruce Stillman, Huilin Li

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

The eukaryotic origin recognition complex (ORC) interacts with and remodels origins of DNA replication prior to initiation in S phase. Here, we report a single-particle cryo-EM-derived structure of the supramolecular assembly comprising Saccharomyces cerevisiae ORC, the replication initiation factor Cdc6, and double-stranded ARS1 origin DNA in the presence of ATPγS. The six subunits of ORC are arranged as Orc1:Orc4:Orc5:Orc2:Orc3, with Orc6 binding to Orc2. Cdc6 binding changes the conformation of ORC, in particular reorienting the Orc1 N-terminal BAH domain. Segmentation of the 3D map of ORC-Cdc6 on DNA and docking with the crystal structure of the homologous archaeal Orc1/Cdc6 protein suggest an origin DNA binding model in which the DNA tracks along the interior surface of the crescent-like ORC. Thus, ORC bends and wraps the DNA. This model is consistent with the observation that binding of a single Cdc6 extends the ORC footprint on origin DNA from both ends.

Original languageEnglish
Pages (from-to)534-544
Number of pages11
JournalStructure
Volume20
Issue number3
DOIs
Publication statusPublished - Mar 7 2012

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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