Parole terms for a killer: directing caspase3/CAD induced DNA strand breaks to coordinate changes in gene expression.
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.
Larsen
Brian D
BD
Ottawa Hospital Research Institute, Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital, Ottawa, ON Canada.
Megeney
Lynn A
LA
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D065150:Cellular Reprogramming / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D003851:Deoxyribonucleases / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D015398:Signal Transduction / Q000235:genetics
D003851:Deoxyribonucleases; D053148:Caspase 3