Cdc45 Is a Critical Effector of Myc-Dependent DNA Replication Stress

68Citations
Citations of this article
141Readers
Mendeley users who have this article in their library.

Abstract

c-Myc oncogenic activity is thought to be mediated in part by its ability to generate DNA replication stress and subsequent genomic instability when deregulated. Previous studies have demonstrated a nontranscriptional role for c-Myc in regulating DNA replication. Here, we analyze the mechanisms by which c-Myc deregulation generates DNA replication stress. We find that overexpression of c-Myc alters the spatiotemporal program of replication initiation by increasing the density of early-replicating origins. We further show that c-Myc deregulation results inelevated replication-fork stalling or collapse and subsequent DNA damage. Notably, these phenotypes are independent of RNA transcription. Finally, we demonstrate that overexpression of Cdc45 recapitulates all c-Myc-induced replication and damage phenotypes and that Cdc45 and GINS function downstream of Myc. © 2013 The Authors.

Cite

CITATION STYLE

APA

Srinivasan, S. V., Dominguez-Sola, D., Wang, L. C., Hyrien, O., & Gautier, J. (2013). Cdc45 Is a Critical Effector of Myc-Dependent DNA Replication Stress. Cell Reports, 3(5), 1629–1639. https://doi.org/10.1016/j.celrep.2013.04.002

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free