Transient association of MCM complex proteins with the nuclear matrix during initiation of mammalian DNA replication

Cell Cycle. 2015;14(3):333-41. doi: 10.4161/15384101.2014.980647.

Abstract

The minichromosome maintenance complex (MCM2-7) is the putative DNA helicase in eukaryotes, and essential for DNA replication. By applying serial extractions to mammalian cells synchronized by release from quiescence, we reveal dynamic changes to the sub-nuclear compartmentalization of MCM2 as cells pass through late G1 and early S phase, identifying a brief window when MCM2 becomes transiently attached to the nuclear-matrix. The data distinguish 3 states that correspond to loose association with chromatin prior to DNA replication, transient highly stable binding to the nuclear-matrix coincident with initiation, and a post-initiation phase when MCM2 remains tightly associated with chromatin but not the nuclear-matrix. The data suggests that functional MCM complex loading takes place at the nuclear-matrix.

Keywords: DNA replication; MCM, Minichromosome maintenance; MCM2-7, nuclear matrix; NM, Nuclear matrix; cell cycle; initiation; minichromosome maintenance complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Chromatin / metabolism
  • DNA Replication* / drug effects
  • Deoxyribonuclease I / metabolism
  • G1 Phase / drug effects
  • Mice
  • Minichromosome Maintenance Proteins / metabolism*
  • Nuclear Matrix / drug effects
  • Nuclear Matrix / metabolism*
  • Protein Binding / drug effects
  • S Phase / drug effects
  • Succinimides / pharmacology

Substances

  • Chromatin
  • Succinimides
  • Deoxyribonuclease I
  • Minichromosome Maintenance Proteins
  • dithiobis(succinimidylpropionate)