Non-transcriptional control of DNA replication by c-Myc

Nature. 2007 Jul 26;448(7152):445-51. doi: 10.1038/nature05953. Epub 2007 Jun 27.

Abstract

The c-Myc proto-oncogene encodes a transcription factor that is essential for cell growth and proliferation and is broadly implicated in tumorigenesis. However, the biological functions required by c-Myc to induce oncogenesis remain elusive. Here we show that c-Myc has a direct role in the control of DNA replication. c-Myc interacts with the pre-replicative complex and localizes to early sites of DNA synthesis. Depletion of c-Myc from mammalian (human and mouse) cells as well as from Xenopus cell-free extracts, which are devoid of RNA transcription, demonstrates a non-transcriptional role for c-Myc in the initiation of DNA replication. Overexpression of c-Myc causes increased replication origin activity with subsequent DNA damage and checkpoint activation. These findings identify a critical function of c-Myc in DNA replication and suggest a novel mechanism for its normal and oncogenic functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Extracts
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • DNA Damage / genetics
  • DNA Replication / genetics*
  • Fibroblasts
  • HeLa Cells
  • Humans
  • Mice
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / deficiency
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Replication Origin / genetics*
  • Transcription, Genetic
  • Xenopus

Substances

  • Cell Extracts
  • Multiprotein Complexes
  • Proto-Oncogene Proteins c-myc