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Nature July 26, 2007; 448 (7152): 445-51.

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

Dominguez-Sola D , Ying CY , Grandori C , Ruggiero L , Chen B , Li M , Galloway DA , Gu W , Gautier J , Dalla-Favera R .

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.

PubMed ID: 17597761
Article link: Nature

Species referenced: Xenopus
Genes referenced: abcc6 atm cdc45 gmnn h2ac21 h2axl il17f mcm6 myc pola1
GO keywords: cell proliferation [+]

Disease Ontology terms: Burkitt lymphoma

Article Images: [+] show captions