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| Subject Categories: Cell Cycle |
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| The EMBO Journal
(2006) 25, 2814–2827, doi:10.1038/sj.emboj.7601168 Published online 8 June 2006 |
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| Misorientation and reduced stretching of aligned sister kinetochores promote chromosome missegregation in EB1- or APC-depleted cells |
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| V M Draviam1, I Shapiro1, B Aldridge2 and P K Sorger1, 2 |
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1 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA 2 Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA, USA To whom correspondence should be addressed P K Sorger, Department of Biology, 68-371 MIT, 77 Mass Avenue, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Tel.: +1 617 252 1806/1648; Fax: +1 617 253 8550; E-mail: psorger@mit.edu Received 21 September 2005; Accepted 4 May 2006; Published online 8 June 2006. |
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| Abstract |
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| The correct formation of stable but dynamic links between chromosomes and spindle microtubules (MTs) is essential for accurate chromosome segregation. However, the molecular mechanisms by which kinetochores bind MTs and checkpoints monitor this binding remain poorly understood. In this paper, we analyze the functions of six kinetochore-bound MT-associated proteins (kMAPs) using RNAi, live-cell microscopy and quantitative image analysis. We find that RNAi-mediated depletion of two kMAPs, the adenomatous polyposis coli protein (APC) and its binding partner, EB1, are unusual in affecting the movement and orientation of paired sister chromatids at the metaphase plate without perturbing kinetochore–MT attachment per se. Quantitative analysis shows that misorientation phenotypes in metaphase are uniform across chromatid pairs even though chromosomal loss (CIN) during anaphase is sporadic. However, errors in kinetochore function generated by APC or EB1 depletion are detected poorly if at all by the spindle checkpoint, even though they cause chromosome missegregation. We propose that impaired EB1 or APC function generates lesions invisible to the spindle checkpoint and thereby promotes low levels of CIN expected to fuel aneuploidy and possibly tumorigenesis. |
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| Keywords: aneuploidy, chromosome segregation, kinetochore, microtubule-associated protein |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSRanBP2 resolves sister centromeres Nature Cell Biology News and Views (01 May 2008) Nature Cell Biology News and Views (01 Nov 2003) RESEARCHA functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling Nature Cell Biology Letter (01 May 2007) A dual role for Bub1 in the spindle checkpoint and chromosome congression The EMBO Journal Article (20 Apr 2005) |
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