Non-transcriptional control of DNA replication by c-Myc

David Dominguez-Sola, Carol Y. Ying, Carla Grandori, Luca Ruggiero, Brenden Chen, Muyang Li, Denise A. Galloway, Wei Gu, Jean Gautier, Riccardo Dalla-Favera

Research output: Contribution to journalArticlepeer-review

531 Scopus citations


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.

Original languageEnglish
Pages (from-to)445-451
Number of pages7
Issue number7152
StatePublished - 26 Jul 2007
Externally publishedYes


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