Como as células humanas mantêm o número correto de cromossomos: mero acaso, fortuita necessidade ou design inteligente?

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Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells

Roshan L. Shrestha, Duccio Conti, Naoka Tamura, Dominique Braun, Revathy A. Ramalingam, Konstanty Cieslinski, Jonas Ries & Viji M. Draviam

Nature Communications 8, Article number: 150 (2017)

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Chromosome segregation Mitosis

Received: 19 August 2016 Accepted: 12 June 2017

Published online: 28 July 2017

Source/Fonte: PMG Biology


Human chromosomes are captured along microtubule walls (lateral attachment) and then tethered to microtubule-ends (end-on attachment) through a multi-step end-on conversion process. Upstream regulators that orchestrate this remarkable change in the plane of kinetochore-microtubule attachment in human cells are not known. By tracking kinetochore movements and using kinetochore markers specific to attachment status, we reveal a spatially defined role for Aurora-B kinase in retarding the end-on conversion process. To understand how Aurora-B activity is counteracted, we compare the roles of two outer-kinetochore bound phosphatases and find that BubR1-associated PP2A, unlike KNL1-associated PP1, plays a significant role in end-on conversion. Finally, we uncover a novel role for Aurora-B regulated Astrin-SKAP complex in ensuring the correct plane of kinetochore-microtubule attachment. Thus, we identify Aurora-B as a key upstream regulator of end-on conversion in human cells and establish a late role for Astrin-SKAP complex in the end-on conversion process.


We thank J. DeLuca for phospho-specific HEC1 antibodies, S. Lens for Mis12-INCENP-GFP and CenpB-INCENP-GFP expression vectors, A. Saurin for KNL1 expression vectors and J. Nilsson for BubR1-expressing cell lines. We thank the Draviam group members and in particular Madeleine Hart for comments on the manuscript. We also thank S. Court, P. Ungerer, U. Matti and A. Sossick for technical and infrastructural support. D.C. is supported through an MRC studentship award (MR/K50127X/1; RG70550) and Cambridge Commonwealth, European and International Trust. This work was supported by research funding from Cancer Research UK Career (C28598/A9787), MRC (MR/K50127X/1; RG70550), Royal Society (JP100104) and QMUL laboratory startup grant.

Author information

Author notes

Roshan L. Shrestha

Present address: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA

Naoka Tamura

Present address: Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK

Roshan L. Shrestha and Duccio Conti contributed equally to this work.


Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK

Roshan L. Shrestha, Duccio Conti, Naoka Tamura, Dominique Braun & Viji M. Draviam

School of Biological and Chemical Sciences, Queen Mary University of London, London, E1 4NS, UK

Duccio Conti, Revathy A. Ramalingam & Viji M. Draviam

European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, Meyerhofstrasse 1, Heidelberg, Germany

Konstanty Cieslinski & Jonas Ries


D.C. contributed to data in Fig. 4, Supplementary Figs. 5, 6 and 7, and the illustration of model in Fig. 6. R.A.R. and N.T. contributed to Supplementary Fig. 1A and reagents in Supplementary Fig. 8B, respectively. J.R., D.C. and K.C. contributed to super-resolution images in Supplementary Fig. 7B. R.L.S. contributed to data in all other figures. Manuscript text was written by V.M.D. and revised together with R.L.S., D.C. and N.T.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Viji M. Draviam.