生物谷報道：c-Myc最初是作為一個原致癌基因發(fā)現(xiàn)的，活躍于很多人類腫瘤中,，但它也是一種轉(zhuǎn)錄因子，是正常細胞生長和增殖所必需的,。它影響基因表達的能力過去曾被認為是其促進腫瘤發(fā)育的手段,，但關(guān)于c-Myc也影響DNA復(fù)制的發(fā)現(xiàn)直接表明，對于它的某些作用應(yīng)有另一種解釋,。通過定位DNA合成點及與復(fù)制前復(fù)合體相結(jié)合,，c-Myc能夠控制DNA復(fù)制：當失控時，同一機制也許還能引起DNA損傷和不正確的細胞增殖,。
原始出處:
Nature 448, 445-451 (26 July 2007) | doi:10.1038/nature05953; Received 9 August 2006; Accepted 18 May 2007; Published online 27 June 2007
Non-transcriptional control of DNA replication by c-Myc
David Dominguez-Sola1,3, Carol Y. Ying1,3, Carla Grandori2,4, Luca Ruggiero1, Brenden Chen1, Muyang Li1, Denise A. Galloway2, Wei Gu1, Jean Gautier1,3 & Riccardo Dalla-Favera1,3
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
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
These authors contributed equally to this work.
Present address: Rosetta Inpharmatics, Merck, Seattle, Washington 98109, USA.
Correspondence to: Jean Gautier1,3Riccardo Dalla-Favera1,3 Correspondence and requests for materials should be addressed to R.D.-F. (Email: [email protected]) or J.G. (Email: [email protected]).
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.
