Unscheduled expression of CDC25B in S-phase leads to replicative stress and DNA damage.

Molecular Cancer
Béatrix BuglerBernard Ducommun

Abstract

CDC25B phosphatase is a cell cycle regulator that plays a critical role in checkpoint control. Up-regulation of CDC25B expression has been documented in a variety of human cancers, however, the relationships with the alteration of the molecular mechanisms that lead to oncogenesis still remain unclear. To address this issue we have investigated, in model cell lines, the consequences of unscheduled and elevated CDC25B levels. We report that increased CDC25B expression leads to DNA damage in the absence of genotoxic treatment. H2AX phosphorylation is detected in S-phase cells and requires active replication. We also report that CDC25B expression impairs DNA replication and results in an increased recruitment of the CDC45 replication factor onto chromatin. Finally, we observed chromosomal aberrations that are also enhanced upon CDC25B expression. Overall, our results demonstrate that a moderate and unscheduled increase in CDC25B level, as observed in a number of human tumours, is sufficient to overcome the S-phase checkpoint efficiency thus leading to replicative stress and genomic instability.

References

Sep 15, 1995·Science·K GalaktionovD Beach
Aug 8, 1996·Nature·K GalaktionovD Beach
Jun 4, 1998·International Journal of Cancer. Journal International Du Cancer·P A Garner-Hamrick, C Fisher
Aug 12, 1999·The Journal of Cell Biology·C KarlssonJ Pines
May 24, 2000·Oncogene·N DavezacB Ducommun
Jun 28, 2002·The Journal of Biological Chemistry·Melissa C EdwardsJohannes C Walter
Jul 15, 2003·Molecular Biology of the Cell·Patric TurowskiNed J C Lamb
Jun 29, 2004·Nature Cell Biology·David ShechterJean Gautier
Jul 21, 2004·Cancer Cell·Michael H LamJeffrey M Rosen
Aug 25, 2004·Chemistry & Biology·K Kristjánsdóttir, J Rudolph
Sep 8, 2004·Molecular Cell·Marcel A T M van VugtRené H Medema
Oct 1, 2004·Journal of Cell Science·Arne LindqvistChristina Karlsson Rosenthal
Mar 9, 2005·The Journal of Cell Biology·Mark G Alexandrow, Joyce L Hamlin
Apr 20, 2005·Oncogene·David Y Takeda, Anindya Dutta
Apr 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yoshinori KanemoriNoriyuki Sagata
Sep 15, 2005·The Journal of Biological Chemistry·Hiroyuki NiidaMakoto Nakanishi
Oct 12, 2005·The Journal of Cell Biology·Arne LindqvistChristina Karlsson Rosenthal
Apr 4, 2006·Molecular and Cellular Biology·Eva PetermannKeith W Caldecott
Jul 5, 2006·Molecular Cancer Therapeutics·Béatrix BuglerBernard Ducommun
Apr 6, 2007·Cancer Research·Pallavi Bansal, John S Lazo
May 12, 2007·The EMBO Journal·Apolinar Maya-MendozaDean A Jackson
Jun 15, 2007·Nature Reviews. Cancer·Rose BoutrosBernard Ducommun
Jun 19, 2007·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Christina BauerschmidtFrank Grosse
Jun 29, 2007·Nature·David Dominguez-SolaRiccardo Dalla-Favera
Jul 31, 2007·FEBS Letters·Charlotte Esmenjaud-MailhatBernard Ducommun
Dec 20, 2007·Cancer Research·Rose BoutrosBernard Ducommun
Mar 8, 2008·Science·Thanos D HalazonetisJiri Bartek
Jun 21, 2008·International Journal of Cancer. Journal International Du Cancer·Maria Giulia CangiClaudio Doglioni
Dec 17, 2008·Anti-cancer Agents in Medicinal Chemistry·Bernadette Aressy, Bernard Ducommun
Dec 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Deborah WilskerFred Bunz
Feb 25, 2009·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid

❮ Previous
Next ❯

Citations

Aug 27, 2013·Nature·Antonio TedeschiJan-Michael Peters
Jul 6, 2014·Stem Cells and Development·Sang-Wook YoonKyung-Soon Park
Oct 11, 2013·Journal of Virology·Olivia PerwitasariRalph A Tripp
Jun 26, 2015·Journal of Bioscience and Bioengineering·Rima MatsuyamaTakeshi Omasa
Jun 27, 2019·Molecular Carcinogenesis·Jenan Al-MatouqLaura A Hansen
Oct 12, 2019·FEBS Letters·Adrijana Crncec, Helfrid Hochegger
Jan 14, 2020·Genetics and Molecular Biology·Luiza M F Primo, Leonardo K Teixeira

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
chromosomal aberrations
transfection

Software Mentioned

Image J
ImageJ
MetaMorph

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.