Research

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

Béatrix Bugler^1,2 , Estelle Schmitt^1,2,4 , Bernadette Aressy^1,2 and Bernard Ducommun^1,2,3

¹  Université de Toulouse, LBCMCP, 118 route de Narbonne, F-31062 Toulouse, France

²  CNRS, LBCMCP-UMR5088, F-31062 Toulouse, France

³  CHU Purpan, TSA 40031, F-31059 Toulouse, France

⁴  Notre Dame Hospital and Montreal Cancer Institute, Montreal H2L 4 M1, Canada

author email corresponding author email

Molecular Cancer 2010, 9:29doi:10.1186/1476-4598-9-29

Published:	4 February 2010

Abstract

Background

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.

Results

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.

Conclusion

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.