Fbxo28 promotes mitotic progression and regulates topoisomerase IIα-dependent DNA decatenation.
Fiche publication
Date publication
décembre 2016
Journal
Cell cycle (Georgetown, Tex.)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DELECLUSE Henri-Jacques
Tous les auteurs :
Kratz AS, Richter KT, Schlosser YT, Schmitt M, Shumilov A, Delecluse HJ, Hoffmann I
Lien Pubmed
Résumé
Topoisomerase IIα is an essential enzyme that resolves topological constraints in genomic DNA. It functions in disentangling intertwined chromosomes during anaphase leading to chromosome segregation thus preserving genomic stability. Here we describe a previously unrecognized mechanism regulating topoisomerase IIα activity that is dependent on the F-box protein Fbxo28. We find that Fbxo28, an evolutionarily conserved protein, is required for proper mitotic progression. Interfering with Fbxo28 function leads to a delay in metaphase-to-anaphase progression resulting in mitotic defects as lagging chromosomes, multipolar spindles and multinucleation. Furthermore, we find that Fbxo28 interacts and colocalizes with topoisomerase IIα throughout the cell cycle. Depletion of Fbxo28 results in an increase in topoisomerase IIα-dependent DNA decatenation activity. Interestingly, blocking the interaction between Fbxo28 and topoisomerase IIα also results in multinucleated cells. Our findings suggest that Fbxo28 regulates topoisomerase IIα decatenation activity and plays an important role in maintaining genomic stability.
Référence
Cell Cycle. 2016 Dec;15(24):3419-3431