Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-289

Pandey, R; Heeger, S; Lehner, C F (2007). Rapid effects of acute anoxia on spindle kinetochore interactions activate the mitotic spindle checkpoint. Journal of Cell Science, 120(16):2807-2818.

Published Version
View at publisher


The dramatic chromosome instability in certain tumors might reflect a synergy of spindle checkpoint defects with hypoxic conditions. In Caenorhabditis elegans and Drosophila melanogaster, spindle checkpoint activation has been implicated in the response to acute anoxia. The activation mechanism is unknown. Our analyses in D. melanogaster demonstrate that oxygen deprivation affects microtubule organization within minutes. The rapid effects of anoxia are identical in wild-type and spindle checkpoint-deficient Mps1 mutant embryos. Therefore, the anoxia effects on the mitotic spindle are not a secondary consequence of spindle checkpoint activation. Some motor, centrosome and kinetochore proteins (dynein, Kin-8, Cnn, TACC, Cenp-C, Nuf2) are rapidly relocalized after oxygen deprivation. Kinetochores congress inefficiently into the metaphase plate and do not experience normal pulling forces. Spindle checkpoint proteins accumulate mainly within the spindle midzone and inhibit anaphase onset. In checkpoint-deficient embryos, mitosis is still completed after oxygen deprivation, although accompanied by massive chromosome missegregation. Inhibitors of oxidative phosphorylation mimic anoxia effects. We conclude that oxygen deprivation impairs the chromosome segregation machinery more rapidly than spindle checkpoint function. Although involving adenosine triphosphate (ATP)-consuming kinases, the spindle checkpoint can therefore be activated by spindle damage in response to acute anoxia and protect against aneuploidies.


16 citations in Web of Science®
15 citations in Scopus®
Google Scholar™



66 downloads since deposited on 11 Feb 2008
13 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Date:15 August 2007
Deposited On:11 Feb 2008 12:14
Last Modified:05 Apr 2016 12:13
Publisher:Company of Biologists
Additional Information:Free full text article
Publisher DOI:10.1242/jcs.007690
PubMed ID:17652159

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page