A small molecule inhibitor of polycomb repressive complex 1 inhibits ubiquitin signaling at DNA double-strand breaks
IH Ismail, D McDonald, H Strickfaden, Z Xu… - Journal of Biological …, 2013 - ASBMB
Polycomb-repressive complex 1 (PRC1)-mediated histone ubiquitylation plays an important
role in aberrant gene silencing in human cancers and is a potential target for cancer therapy.
Here we show that 2-pyridine-3-yl-methylene-indan-1, 3-dione (PRT4165) is a potent
inhibitor of PRC1-mediated H2A ubiquitylation in vivo and in vitro. The drug also inhibits the
accumulation of all detectable ubiquitin at sites of DNA double-strand breaks (DSBs), the
retention of several DNA damage response proteins in foci that form around DSBs, and the …
role in aberrant gene silencing in human cancers and is a potential target for cancer therapy.
Here we show that 2-pyridine-3-yl-methylene-indan-1, 3-dione (PRT4165) is a potent
inhibitor of PRC1-mediated H2A ubiquitylation in vivo and in vitro. The drug also inhibits the
accumulation of all detectable ubiquitin at sites of DNA double-strand breaks (DSBs), the
retention of several DNA damage response proteins in foci that form around DSBs, and the …
