c-Myc对DNA复制影响作用的解释

    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

1. 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
2. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
3. These authors contributed equally to this work.
4. 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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