Dual role of Topoisomerase II in centromere resolution and Aurora B activity

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Coelho, PA (Author) Other; Queiroz Machado, J (Author) Other; Alexandre Carmo (Author) Other; Moutinho Pereira, S (Author) Other; Helder Maiato (Author) FMUP; Sunkel, CE (Author) ICBAS

Journal

Title: PLoS Biology

Vol. 6

Pages: 1758-1777

ISSN: 1544-9173

Publisher: Public Library of Science

Indexing

ISI Web of Knowledge - 61 Citations

Scopus - 61 Citations

Other information

Authenticus ID: P-003-XKE

DOI: 10.1371/journal.pbio.0060207

Abstract (EN): Chromosome segregation requires sister chromatid resolution. Condensins are essential for this process since they organize an axial structure where topoisomerase II can work. How sister chromatid separation is coordinated with chromosome condensation and decatenation activity remains unknown. We combined four-dimensional (4D) microscopy, RNA interference (RNAi), and biochemical analyses to show that topoisomerase II plays an essential role in this process. Either depletion of topoisomerase II or exposure to specific anti-topoisomerase II inhibitors causes centromere nondisjunction, associated with syntelic chromosome attachments. However, cells degrade cohesins and timely exit mitosis after satisfying the spindle assembly checkpoint. Moreover, in topoisomerase II-depleted cells, Aurora B and INCENP fail to transfer to the central spindle in late mitosis and remain tightly associated with centromeres of nondisjoined sister chromatids. Also, in topoisomerase II-depleted cells, Aurora B shows significantly reduced kinase activity both in S2 and HeLa cells. Codepletion of BubR1 in S2 cells restores Aurora B kinase activity, and consequently, most syntelic attachments are released. Taken together, our results support that topoisomerase II ensures proper sister chromatid separation through a direct role in centromere resolution and prevents incorrect microtubule-kinetochore attachments by allowing proper activation of Aurora B kinase.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 20