c-Myc对DNA复制影响作用的解释
毕业论文
生物谷报道：c-Myc最初是作为1个原致癌基因发现的，活跃于很多人类肿瘤中，但它也是1种转录因子，是正常细胞生长和增殖所必需的。它影响基因表达的能力过去曾被认为是其促进肿瘤发育的.手段，但关于c-Myc也影响DNA复制的发现直接表明，对于它的某些作用应有另1种解释。通过定位DNA合成点及与复制前复合体相结合，c-Myc能够控制DNA复制：当失控时，同1机制也许还能引起DNA损伤和不正确的细胞增殖。
原始出处:
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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