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Published online 12 June 2006. doi:10.1083/jcb.200511129
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 173, Number 6, 893-903
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Article

Transcription of ribosomal genes can cause nondisjunction



Felix Machín1, Jordi Torres-Rosell1, Giacomo De Piccoli1, Jesús A. Carballo2, Rita S. Cha2, Adam Jarmuz1, and Luis Aragón1

1 Cell Cycle Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, England, UK
2 Division of Yeast Genetics, National Institute for Medical Research, London NW7 1AA, England, UK

Correspondence to Luis Aragon: luis.aragon{at}csc.mrc.ac.uk

Mitotic disjunction of the repetitive ribosomal DNA (rDNA) involves specialized segregation mechanisms dependent on the conserved phosphatase Cdc14. The reason behind this requirement is unknown. We show that rDNA segregation requires Cdc14 partly because of its physical length but most importantly because a fraction of ribosomal RNA (rRNA) genes are transcribed at very high rates. We show that cells cannot segregate rDNA without Cdc14 unless they undergo genetic rearrangements that reduce rDNA copy number. We then demonstrate that cells with normal length rDNA arrays can segregate rDNA in the absence of Cdc14 as long as rRNA genes are not transcribed. In addition, our study uncovers an unexpected role for the replication barrier protein Fob1 in rDNA segregation that is independent of Cdc14. These findings demonstrate that highly transcribed loci can cause chromosome nondisjunction.

Abbreviations used in this paper: ERC, extrachromosomal ribosomal circle; FEAR, Cdc14 early anaphase release; MEN, mitotic exit network; PFGE, pulsed-field gel electrophoresis; rDNA, ribosomal DNA; RFB, replication fork barrier.


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