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E2F4 Function in G2 Maintaining G2-arrest to Prevent Mitotic Entry with Damaged DNA
Dragos Plesca, Meredith E. Crosby, Damodar Gupta and Alex Almasan
volume 6 | issue 10
15 May 2007Pages: 1147 - 1152
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Mammalian cells undergo cell cycle arrest in response to DNA damage through multiple checkpoint mechanisms. One such checkpoint pathway maintains genomic integrity by delaying mitotic progression in response to genotoxic stress. Transition though the G2 phase and entry into mitosis is considered to be regulated primarily by Cyclin B1 and its associated catalytically active partner Cdk1. While not necessary for its initiation, the p130 and Rb-dependent target genes have emerged as being important for stable maintenance of a G2 arrest. It was recently demonstrated that by interacting with p130, E2F4 is present in the nuclei and plays a key role in the maintenance of this stable G2 arrest. Increased E2F4 levels and its translocation to the nucleus following genotoxic stress results in down-regulation of many mitotic genes and as a result promote a G0-like state. Irradiation of E2F4-depleted cells leads to enhanced cellular DNA double-strand breaks that may be measured by comet assays. It also results in cell death that is characterized by caspase activation, sub-G1 and sub-G2 DNA content, and decreased clonogenic cell survival. Here we review these recent findings and discuss the mechanisms of G2 phase checkpoint activation and maintenance with a particular focus on E2F4.
Authors
Dragos Plesca
The Lerner Research Institute, Cleveland, Ohio
Meredith E. Crosby
Case Western Reserve University, Cleveland, Ohio
Damodar Gupta
The Lerner Research Institute, Cleveland, Ohio
Alex Almasan
The Lerner Research Institute, Cleveland, Ohio
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.