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

Non-transcriptional control of DNA replication by c-Myc.

Author information

1
Institute for Cancer Genetics, Department of Genetics and Development and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York 10032, USA.

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.

PMID:
17597761
DOI:
10.1038/nature05953
[Indexed for MEDLINE]

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