The involvement of acidic nucleoplasmic DNA-binding protein (And-1) in the regulation of prereplicative complex (pre-RC) assembly in human cells

J Biol Chem. 2012 Dec 14;287(51):42469-79. doi: 10.1074/jbc.M112.404277. Epub 2012 Oct 23.

Abstract

DNA replication in all eukaryotes starts with the process of loading the replicative helicase MCM2-7 onto chromatin during late mitosis of the cell cycle. MCM2-7 is a key component of the prereplicative complex (pre-RC), which is loaded onto chromatin by the concerted action of origin recognition complex, Cdc6, and Cdt1. Here, we demonstrate that And-1 is assembled onto chromatin in late mitosis and early G(1) phase before the assembly of pre-RC in human cells. And-1 forms complexes with MCM2-7 to facilitate the assembly of MCM2-7 onto chromatin at replication origins in late mitosis and G(1) phase. We also present data to show that depletion of And-1 significantly reduces the interaction between Cdt1 and MCM7 in G(1) phase cells. Thus, human And-1 facilitates loading of the MCM2-7 helicase onto chromatin during the assembly of pre-RC.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Chromatin / metabolism
  • DNA Replication*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • G1 Phase
  • Histone Acetyltransferases / metabolism
  • Histones / metabolism
  • Humans
  • Minichromosome Maintenance Complex Component 2
  • Minichromosome Maintenance Complex Component 7
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Replication Origin
  • Telophase

Substances

  • CDT1 protein, human
  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • Nuclear Proteins
  • WDHD1 protein, human
  • Histone Acetyltransferases
  • KAT7 protein, human
  • MCM2 protein, human
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 2
  • Minichromosome Maintenance Complex Component 7