Sign up for Table of Contents Alerts.
Email this page
Print this page
Report
Upregulation of Error-Prone DNA Polymerases Beta and Kappa Slows Down Fork Progression Without Activating the Replication Checkpoint
Marie-Jeanne Pillaire, Rémy Betous, Chiara Conti, Jerzy Czaplicki, Philippe Pasero, Aaron Bensimon, Christophe Cazaux and Jean-Sébastien Hoffmann
volume 6 | issue 4
15 February 2007Pages: 471 - 477
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.
There is rising evidence that cancer development is associated from its earliest stages with DNA replication stress, a major source of spontaneous genomic instability. However, the origin of these replication defects has remained unclear. We have investigated the consequences of upregulating error-prone DNA polymerases (pol) beta and kappa on chromosomal DNA replication. These enzymes are misregulated in different types of cancers and induce major chromosomal instabilities when overexpressed at low levels. Here, we have used DNA combing to show that a moderate overexpression of pol beta or pol kappa is sufficient to impede replication fork progression and to promote the activation of additional replication origins. Interestingly, alterations of the normal replication program induced by excess error-prone polymerases were not detected by the replication checkpoint. We therefore propose that upregulation of error-prone DNA polymerases induces a checkpoint-blind replication stress that contributes to genomic instability and to cancer development.
Authors
Marie-Jeanne Pillaire
CNRS, Toulouse, France
Rémy Betous
CNRS, Toulouse, France
Chiara Conti
National Cancer Institute; Bethesda, MD
Jerzy Czaplicki
CNRS, Toulouse, France
Philippe Pasero
IGMM - CNRS UMR5535
Aaron Bensimon
Institute Pasteu, Paris France
Christophe Cazaux
CNRS, Toulouse, France
Jean-Sébastien Hoffmann
CNRS, Toulouse, France
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.