E2F1 and orofacial cleft: Therefore, the combined effects of transcriptional dysregulation and of environmental factors must be critical in a tissue-and time-specific manner, which can explain why orofacial clefts have not been observed in knockout animal models for pivotal DNA repair genes, including E2F1. Under these circumstances, we hypothesise that the inability to appropriately deal with DNA damage would result in disturbances in cell proliferation and/or lead to apoptosis, disrupting lip and palate morphogenesis.