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c-Myc對DNA復(fù)制影響作用的解釋
畢業(yè)論文
生物谷報道:c-Myc最初是作為1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1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1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1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: rd10@columbia.edu) or J.G. (Email: jg130@columbia.edu).
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.
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