Cell proliferation in the absence of E2F1-3

► Lens epithelial cells proliferate in the absence of E2F1-3 during development. ► Loss of E2F1-3 alters expression of genes required for lens differentiation. ► E2F loss causes activation of p53 signaling, DNA double-strand breaks and apoptosis. ► Cell cycle-dependent genes are upregulated with ablation of E2F “activators”. ► Deletion of E2F3 rescues hallmark phenotypic defects caused by loss of Rb.