ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4

Abstract

During the final stage of cell division, cytokinesis, the Aurora-B-dependent abscission checkpoint (NoCut) delays membrane abscission to avoid DNA damage and aneuploidy in cells with chromosome segregation defects. This arrest depends on Aurora-B-mediated phosphorylation of CHMP4C, a component of the endosomal sorting complex required for transport (ESCRT) machinery that mediates abscission, but the mechanism remains unknown. Here we describe ANCHR (Abscission/NoCut Checkpoint Regulator; ZFYVE19) as a key regulator of the abscission checkpoint, functioning through the most downstream component of the ESCRT machinery, the ATPase VPS4. In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing and prevent multinucleation in an Aurora-B-dependent manner. This association prevents VPS4 relocalization to the abscission zone and is relieved following inactivation of Aurora B to allow abscission. We propose that the abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring.

Structure, function and regulation of jade family PHD finger 1 (JADE1)

“…Recently, it has been reported that the novel Abscission/NoCut Checkpoint Regulator (ANCHR) protein functions in Aurora-B-dependent abscission checkpoint control in HeLa cells 46 . Interestingly, ANCHR polypeptide includes FYVE and RING finger domains, while PHD2 finger of JADE1S may have structural similarities with the RING finger.…”

PKCɛ switches Aurora B specificity to exit the abscission checkpoint

“…The existence of a final ‘NoCut' checkpoint before exit from cytokinesis has been defined by a number of groups in yeast, worms and mammalian systems1234567. This checkpoint, operating at the point of no return for precise and successful self-renewal, is dependent on Aurora B kinase activity and is engaged by the presence of chromatin trapped in the cytokinesis furrow.…”

WD Repeat-containing Protein 5 (WDR5) Localizes to the Midbody and Regulates Abscission

“…Although ϳ8% multinucleation is observed in WDR5 knockdown clones 6 and 8, our live cell imaging data did not reveal any instances of furrow regression in control or WDR5 knockdown stable lines (n ϭ 13-21 cells per group). It is worth noting that a recent study indicates that even if depletion of a protein yields 5-10% multinucleation, the rate of regression could be as low as ϳ1%, and it may be restricted to a minor subset of telophase cells, for example those containing lagging chromosomes (51).…”