BMI1, ATM and DDR

The polycomb group protein BMI1 is a component of the polycomb repressive complex 1 (PRC1). Although lacking enzymatic activity, BMI1 makes an important contribution to the intrinsic E3 ubiquitin ligase activity of PRC1 via binding of the catalytic subunit RING2. PRC1 catalyzes mono-ubiquitination of histone H2A at lysine 119 (H2AK119Ub), a well-recognized epigenetic marker associated with gene silencing [1]. A well-studied locus suppressed by BMI1 is ARF/INK4A, which encodes two tumor suppressors p16INK4A and p14/p19ARF with well-demonstrated functions in activating the pRb and p53 pathway, respectively. This suppression thus plays a major role in BMI1-mediated maintenance of the self-renewal of hematopoietic stem cells (HSCs), neural stem cells (NSCs), stem cells of other tissues, and most importantly