Kinetochore motors drive congression of peripheral polar chromosomes by overcoming random arm-ejection forces

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Marin Barisic (Author) Other; Paulo Aguiar (Author) FMUP; Stephan Geley (Author) Other; Helder Maiato (Author) Other

Journal

Title: Nature Cell Biology

Vol. 16

Pages: 1249-U259

ISSN: 1465-7392

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 92 Citations

Scopus - 95 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-00A-1RM

DOI: 10.1038/ncb3060

Abstract (EN): Accurate chromosome segregation during cell division in metazoans relies on proper chromosome congression at the equator. Chromosome congression is achieved after bi-orientation to both spindle poles shortly after nuclear envelope breakdown, or by the coordinated action of motor proteins that slide misaligned chromosomes along pre-existing spindle microtubules(1). These proteins include the minus-end-directed kinetochore motor dynein(2-5), and the plus-end-directed motors CENP-E at kinetochores(6,7) and chromokinesins on chromosome arms(8-11). However, how these opposite and spatially distinct activities are coordinated to drive chromosome congression remains unknown. Here we used RNAi, chemical inhibition, kinetochore tracking and laser microsurgery to uncover the functional hierarchy between kinetochore and arm-associated motors, exclusively required for congression of peripheral polar chromosomes in human cells. We show that dynein poleward force counteracts chromokinesins to prevent stabilization of immature/incorrect end-on kinetochore microtubule attachments and random ejection of polar chromosomes. At the poles, CENP-E becomes dominant over dynein and chromokinesins to bias chromosome ejection towards the equator. Thus, dynein and CENP-E at kinetochores drive congression of peripheral polar chromosomes by preventing arm-ejection forces mediated by chromokinesins from working in the wrong direction.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14