Parole terms for a killer: directing caspase3/CAD induced DNA strand breaks to coordinate changes in gene expression

Abstract

In a series of discoveries over the preceding decade, a number of laboratories have unequivocally established that apoptotic proteins and pathways are well conserved cell fate determinants, which act independent of a cell death response. Within this context, the role for apoptotic proteins in the induction of cell differentiation has been widely documented. Despite these discoveries, little information has been forthcoming regarding a conserved mechanism by which apoptotic proteins achieve this non-death outcome. In the following discussion, we will explore the premise that the penultimate step in apoptosis, genome wide DNA damage/strand breaks act as a conserved genomic reprogramming event necessary for cell differentiation (Larsen et al. Proc Natl Acad Sci USA 2010; 107:4230-5). Moreover, we hypothesis that directed DNA damage, as mediated by known apoptotic proteins, may participate in numerous forms of regulated gene expression.

Figure 1

Caspase 3 activation balances the dissemination of CAD induced DNA strand breaks for gene reprogramming or fragmentation. This model depicts several factors that may regulate CAD induced DNA strand breaks in physiologic and apoptotic conditions.