Structure of the origin recognition complex bound to DNA replication origin

Nature. 2018 Jul;559(7713):217-222. doi: 10.1038/s41586-018-0293-x. Epub 2018 Jul 4.

Abstract

The six-subunit origin recognition complex (ORC) binds to DNA to mark the site for the initiation of replication in eukaryotes. Here we report a 3 Å cryo-electron microscopy structure of the Saccharomyces cerevisiae ORC bound to a 72-base-pair origin DNA sequence that contains the ARS consensus sequence (ACS) and the B1 element. The ORC encircles DNA through extensive interactions with both phosphate backbone and bases, and bends DNA at the ACS and B1 sites. Specific recognition of thymine residues in the ACS is carried out by a conserved basic amino acid motif of Orc1 in the minor groove, and by a species-specific helical insertion motif of Orc4 in the major groove. Moreover, similar insertions into major and minor grooves are also embedded in the B1 site by basic patch motifs from Orc2 and Orc5, respectively, to contact bases and to bend DNA. This work pinpoints a conserved role of ORC in modulating DNA structure to facilitate origin selection and helicase loading in eukaryotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cryoelectron Microscopy*
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA / ultrastructure
  • Minichromosome Maintenance Proteins / metabolism
  • Models, Molecular
  • Origin Recognition Complex / chemistry*
  • Origin Recognition Complex / metabolism
  • Origin Recognition Complex / ultrastructure*
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Replication Origin*
  • Saccharomyces cerevisiae* / chemistry
  • Saccharomyces cerevisiae* / ultrastructure
  • Substrate Specificity

Substances

  • Origin Recognition Complex
  • Protein Subunits
  • DNA
  • Minichromosome Maintenance Proteins