MYC, PARP1, and Chemoresistance: BIN There, Done That?

Dysregulation of c-MYC plays a critical role in the development of many human cancers. New evidence has uncovered a previously unknown mechanism whereby increased abundance of c-MYC can promote poly(ADP-ribose) polymerase (PARP)-dependent DNA repair pathways and induce relative chemoresistance. The adaptor protein BIN1, whose expression is regulated by c-MYC, interacts with PARP1 and inhibits its enzymatic activity. A model has been proposed in which increased abundance of c-MYC indirectly leads to decreased BIN1 expression, in turn leading to increased PARP activity and resistance to DNA-damaging agents. The clinical implications of these findings are discussed.