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

Molecular Cancer

Research

Béatrix Bugler¹  Bernadette Aressy¹  Bernard Ducommun²  Estelle Schmitt³ 

[1] Université de Toulouse, LBCMCP, 118 route de Narbonne, F-31062, Toulouse, France;CNRS, LBCMCP-UMR5088, F-31062, Toulouse, France;Université de Toulouse, LBCMCP, 118 route de Narbonne, F-31062, Toulouse, France;CNRS, LBCMCP-UMR5088, F-31062, Toulouse, France;CHU Purpan, TSA 40031, F-31059, Toulouse, France;Université de Toulouse, LBCMCP, 118 route de Narbonne, F-31062, Toulouse, France;CNRS, LBCMCP-UMR5088, F-31062, Toulouse, France;Notre Dame Hospital and Montreal Cancer Institute, H2L 4 M1, Montreal, Canada;

关键词: HCT116 Cell;    U2OS Cell;    Roscovitin;    Replication Stress;    CDC25 Phosphatase;   

DOI  :  10.1186/1476-4598-9-29

 received in 2009-09-30, accepted in 2010-02-04,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundCDC25B 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.ResultsWe 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.ConclusionOverall, 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.

【 授权许可】

Unknown   
© Bugler et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.