@article{9e1f5823dbf44575aea0bccad836c330,
title = "Non-transcriptional control of DNA replication by c-Myc",
abstract = "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.",
author = "David Dominguez-Sola and Ying, {Carol Y.} and Carla Grandori and Luca Ruggiero and Brenden Chen and Muyang Li and Galloway, {Denise A.} and Wei Gu and Jean Gautier and Riccardo Dalla-Favera",
note = "Funding Information: Our results indicate that Myc deregulation generates DNA damage and may promote genomic instability by inducing DNA replication stress, strengthening previous observations38–41. This notion is also supported by the dependence on Werner RecQ helicase for Myc-driven proliferation42, and by the requirement for RecQ helicases during replication stress43. These observations can explain the occurrence of genomic alterations, such as gene amplification and illegitimate replication of some loci41, that are consistently associated with Myc deregulation during tumorigenesis. However, in contrast with other oncogenes that may cause DNA re-replication when deregulated44, overexpression of Myc increases the number of active replication origins in the absence of detectable re-replication (data not shown).",
year = "2007",
month = jul,
day = "26",
doi = "10.1038/nature05953",
language = "English",
volume = "448",
pages = "445--451",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7152",
}