Unique Roles of the Non-identical MCM Subunits in DNA Replication Licensing

Mol Cell. 2017 Jul 20;67(2):168-179. doi: 10.1016/j.molcel.2017.06.016.

Abstract

A family of six homologous subunits, Mcm2, -3, -4, -5, -6, and -7, each with its own unique features, forms the catalytic core of the eukaryotic replicative helicase. The necessity of six similar but non-identical subunits has been a mystery since its initial discovery. Recent cryo-EM structures of the Mcm2-7 (MCM) double hexamer, its precursors, and the origin recognition complex (ORC)-Cdc6-Cdt1-Mcm2-7 (OCCM) intermediate showed that each of these subunits plays a distinct role in orchestrating the assembly of the pre-replication complex (pre-RC) by ORC-Cdc6 and Cdt1.

Keywords: Acrobat Model for pre-RC assembly; DNA replication initiation; Mcm2–7; ORC-Cdc6-Cdt1-MCM; cryo-EM structures.

Publication types

  • Review

MeSH terms

  • Animals
  • Catalytic Domain
  • Cell Cycle Proteins / metabolism
  • DNA Replication*
  • Humans
  • Minichromosome Maintenance Proteins / chemistry
  • Minichromosome Maintenance Proteins / metabolism*
  • Minichromosome Maintenance Proteins / ultrastructure
  • Models, Molecular
  • Multiprotein Complexes
  • Nuclear Proteins / metabolism
  • Nucleic Acid Conformation
  • Origin Recognition Complex / chemistry
  • Origin Recognition Complex / metabolism*
  • Origin Recognition Complex / ultrastructure
  • Protein Binding
  • Protein Subunits
  • Structure-Activity Relationship

Substances

  • CDC6 protein, human
  • CDT1 protein, human
  • Cell Cycle Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Origin Recognition Complex
  • Protein Subunits
  • Minichromosome Maintenance Proteins