title: Aurora B-mediated abscission checkpoint protects against tetraploidization.
abstract: Genomic abnormalities are often seen in tumor cells, and tetraploidization, which results from failures during cytokinesis, is presumed to be an early step in cancer formation. Here, we report a cell division control mechanism that prevents tetraploidization in human cells with perturbed chromosome segregation. First, we found that Aurora B inactivation promotes completion of cytokinesis by abscission. Chromosome bridges sustained Aurora B activity to posttelophase stages and thereby delayed abscission at stabilized intercellular canals. This was essential to suppress tetraploidization by furrow regression in a pathway further involving the phosphorylation of mitotic kinesin-like protein 1 (Mklp1). We propose that Aurora B is part of a sensor that responds to unsegregated chromatin at the cleavage site. Our study provides evidence that in human cells abscission is coordinated with the completion of chromosome segregation to protect against tetraploidization by furrow regression.
authors.affiliation: Institute of Biochemistry, Swiss Institute of Technology Zurich, ETHZ, Zurich, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Steigemann
authors.forename: Claudia
authors.initials: C
authors.lastname: Wurzenberger
authors.forename: Michael H A
authors.initials: MH
authors.lastname: Schmitz
authors.forename: Michael
authors.initials: M
authors.lastname: Held
authors.forename: Julien
authors.initials: J
authors.lastname: Guizetti
authors.forename: Sandra
authors.initials: S
authors.lastname: Maar
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Gerlich
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D002455:Cell Division; D020090:Chromosome Segregation; D048749:Cytokinesis; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011003:Ploidies; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C092935:KIF23 protein, human; D008869:Microtubule-Associated Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases