Identification and characterization of a novel component of the human minichromosome maintenance complex

Mol Cell Biol. 2007 Apr;27(8):3044-55. doi: 10.1128/MCB.02384-06. Epub 2007 Feb 12.

Abstract

Minichromosome maintenance (MCM) complex replicative helicase complexes play essential roles in DNA replication in all eukaryotes. Using a tandem affinity purification-tagging approach in human cells, we discovered a form of the MCM complex that contains a previously unstudied protein, MCM binding protein (MCM-BP). MCM-BP is conserved in multicellular eukaryotes and shares limited homology with MCM proteins. MCM-BP formed a complex with MCM3 to MCM7, which excluded MCM2; and, conversely, hexameric complexes of MCM2 to MCM7 lacked MCM-BP, indicating that MCM-BP can replace MCM2 in the MCM complex. MCM-BP-containing complexes exhibited increased stability under experimental conditions relative to those containing MCM2. MCM-BP also formed a complex with the MCM4/6/7 core helicase in vitro, but, unlike MCM2, did not inhibit this helicase activity. A proportion of MCM-BP bound to cellular chromatin in a cell cycle-dependent manner typical of MCM proteins, and, like other MCM subunits, preferentially associated with a cellular origin in G(1) but not in S phase. In addition, down-regulation of MCM-BP decreased the association of MCM4 with chromatin, and the chromatin association of MCM-BP was at least partially dependent on MCM4 and cdc6. The results indicate that multicellular eukaryotes contain two types of hexameric MCM complexes with unique properties and functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromatin / metabolism
  • DNA Helicases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Down-Regulation / genetics
  • G1 Phase
  • Gene Silencing
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Minichromosome Maintenance Complex Component 4
  • Minichromosome Maintenance Complex Component 6
  • Minichromosome Maintenance Complex Component 7
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Transport
  • Recombinant Proteins / metabolism
  • Replication Origin
  • Sequence Analysis, Protein

Substances

  • Adaptor Proteins, Signal Transducing
  • CDC6 protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • MCMBP protein, human
  • Multiprotein Complexes
  • Nuclear Proteins
  • Recombinant Proteins
  • DNA Helicases
  • MCM4 protein, human
  • MCM6 protein, human
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 4
  • Minichromosome Maintenance Complex Component 6
  • Minichromosome Maintenance Complex Component 7