1. ¹Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer (IBMCC), CSIC/Universidad de Salamanca, Salamanca, Spain
2. ²Molecular Pathology Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain

Correspondence: Dr I Sánchez-García, Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Experimental Therapeutics and Translational Oncology Program, CSIC/Universidad de Salamanca, Campus Unamuno, Salamanca 37007, Spain; E-mail: isg@usal.es

³These authors have contributed equally to this work.

Received 14 June 2007; Revised 11 October 2007; Accepted 15 October 2007; Published online 8 January 2008.

Abstract

Snai2-deficient cells are radiosensitive to DNA damage. The function of Snai2 in response to DNA damage seems to be critical for its function in normal development and cancer. Here, we applied a functional genomics approach that combined gene-expression profiling and computational molecular network analysis to obtain global dissection of the Snai2-dependent transcriptional response to DNA damage in primary mouse embryonic fibroblasts (MEFs), which undergo p53-dependent growth arrest in response to DNA damage. Although examination of the response showed that overall expression of p53 target gene expression patterns was similarly altered in both control and Snai2-deficient cells, we have identified and validated candidate Snai2 target genes linked to Snai2 gene function in response to DNA damage. This work defines for the first time the effect of Snai2 on p53 target genes in cells undergoing growth arrest, elucidates the Snai2-dependent molecular network induced by DNA damage, points to novel putative Snai2 targets, and suggest a mechanistic model, which has implications for cancer management.