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
2. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
3. These authors contributed equally to this work.
4. Present address: Rosetta Inpharmatics, Merck, Seattle, Washington 98109, USA.

Correspondence to: Jean Gautier^1,3Riccardo Dalla-Favera^1,3 Correspondence and requests for materials should be addressed to R.D.-F. (Email: rd10@columbia.edu) or J.G. (Email: jg130@columbia.edu).

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.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.