Non-transcriptional control of DNA replication by c-Myc
Non-transcriptional control of DNA replication by c-Myc
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DOI：
10.1038/nature05953
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发表时间：
2007-07-26
期刊：
影响因子：
64.8
通讯作者：
Dalla-Favera, Riccardo
中科院分区：
文献类型：
--
作者：
Dominguez-Sola, David;Ying, Carol Y.;Dalla-Favera, Riccardo
c-Myc原癌基因编码一种转录因子，该转录因子对细胞生长和增殖至关重要，并广泛涉及肿瘤发生。然而，c-Myc诱导肿瘤发生所需的生物学功能仍然难以捉摸。在这里，我们表明c-Myc在控制DNA复制中具有直接作用。c-Myc与复制前复合体相互作用，定位于DNA合成的早期位点。从哺乳动物（人类和小鼠）细胞以及爪蟾无细胞提取物（缺乏RNA转录）中消耗c-Myc，证明了c-Myc在DNA复制起始中的非转录作用。c-Myc过表达导致复制起始活性增加，随后DNA损伤和检查点激活。这些发现确定了c-Myc在DNA复制中的关键功能，并提出了其正常和致癌功能的新机制。
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.