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Deregulation of cyclin e in human cells interferes with prereplication complex assembly

Academic Article
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Overview

authors

  • Ekholm-Reed, S.
  • Mendez, J.
  • Tedesco, D.
  • Zetterberg, A.
  • Stillman, B.
  • Reed, Steven

publication date

  • June 2004

journal

  • Journal of Cell Biology  Journal

abstract

  • Deregulation of cyclin E expression has been associated with a broad spectrum of human malignancies. Analysis of DNA replication in cells constitutively expressing cyclin E at levels similar to those observed in a subset of tumor-derived cell lines indicates that initiation of replication and possibly fork movement are severely impaired. Such cells show a specific defect in loading of initiator proteins Mcm4, Mcm7, and to a lesser degree, Mcm2 onto chromatin during telophase and early G1 when Mcm2-7 are normally recruited to license origins of replication. Because minichromosome maintenance complex proteins are thought to function as a heterohexamer, loading of Mcm2-, Mcm4-, and Mcm7-depleted complexes is likely to underlie the S phase defects observed in cyclin E-deregulated cells, consistent with a role for minichromosome maintenance complex proteins in initiation of replication and fork movement. Cyclin E-mediated impairment of DNA replication provides a potential mechanism for chromosome instability observed as a consequence of cyclin E deregulation.

subject areas

  • Breast Neoplasms
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cyclin E
  • DNA Replication
  • DNA-Binding Proteins
  • Female
  • Flow Cytometry
  • G1 Phase
  • Humans
  • KB Cells
  • Minichromosome Maintenance Complex Component 2
  • Minichromosome Maintenance Complex Component 4
  • Minichromosome Maintenance Complex Component 7
  • Nuclear Proteins
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Research

keywords

  • DNA replicatiom
  • MCM protein
  • cyclin E
  • cyclin E deregulation
  • prereplication complex assembly
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Identity

PubMed Central ID

  • PMC2172392

International Standard Serial Number (ISSN)

  • 0021-9525

Digital Object Identifier (DOI)

  • 10.1083/jcb.200404092

PubMed ID

  • 15197178
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Additional Document Info

start page

  • 789

end page

  • 800

volume

  • 165

issue

  • 6

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