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First published online 8 September 2009
doi: 10.1242/jcs.047944

Journal of Cell Science 122, 3455-3461 (2009)
Published by The Company of Biologists 2009
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Short Report

Aneuploidy in mitosis of PtK1 cells is generated by random loss and nondisjunction of individual chromosomes

Liliana Torosantucci1, Marco De Santis Puzzonia1, Chiara Cenciarelli2, Willem Rens3 and Francesca Degrassi1,*

1 IBPM Institute of Molecular Biology and Pathology, CNR National Research Council, c/o University `La Sapienza', Via degli Apuli 4, 00185 Rome, Italy
2 Department of Biology, University Roma Tre, V.le Marconi 446, 00146, Rome, Italy
3 Centre for Veterinary Science, Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 OES, UK

* Author for correspondence (f.degrassi{at}caspur.it)

Accepted 19 July 2009

Summary

Chromosome lagging at anaphase and migration of both sister chromatids to the same pole, i.e. nondisjunction, are two chromosome-segregation errors producing aneuploid cell progeny. Here, we developed an assay for the simultaneous detection of both chromosome-segregation errors in the marsupial PtK1 cell line by using multiplex fluorescence in situ hybridization with specific painting probes obtained by chromosome flow sorting. No differential susceptibility of the six PtK1 chromosomes to undergo nondisjunction and/or chromosome loss was observed in ana-telophase cells recovering from a nocodazole- or a monastrol-induced mitotic arrest, suggesting that the recurrent presence of specific chromosomes in several cancer types reflects selection effects rather than differential propensities of specific chromosomes to undergo missegregation. Experiments prolonging metaphase duration during drug recovery and inhibiting Aurora-B kinase activity on metaphase-aligned chromosomes provided evidence that some type of merotelic orientations was involved in the origin of both chromosome-segregation errors. Visualization of mero-syntelic kinetochore-microtubule attachments (a merotelic kinetochore in which the thicker microtubule bundle is attached to the same pole to which the sister kinetochore is connected) identified a peculiar malorientation that might participate in the generation of nondisjunction. Our findings imply random missegregation of chromosomes as the initial event in the generation of aneuploidy in mammalian somatic cells.

Key words: Chromosome loss, Nondisjunction, Aneuploidy, Kinetochore-microtubule attachments, Merotelic attachments


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© The Company of Biologists Ltd 2009