Activating the abscission checkpoint: Top2α senses chromatin bridges in cytokinesis: Top2α binds to DNA knots on chromatin bridges to activate the abscission checkpoint in human cells.

Abstract

How chromatin bridges are detected by the abscission checkpoint during mammalian cell division is unknown. Here, we discuss recent findings from our lab showing that the DNA topoisomerase IIα (Top2α) enzyme binds to catenated ("knotted") DNA next to the midbody and forms abortive Top2-DNA cleavage complexes (Top2ccs) on chromatin bridges. Top2ccs are then processed by the proteasome to promote localization of the DNA damage sensor protein Rad17 to Top2-generated double-strand DNA ends on DNA knots. In turn, Rad17 promotes local recruitment of the MRN protein complex and downstream ATM-Chk2-INCENP signaling to delay abscission and prevent chromatin bridge breakage in cytokinesis.