Transcription of ribosomal genes can cause nondisjunction.
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.
Machín
Felix
F
Cell Cycle Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, England, UK.
Torres-Rosell
Jordi
J
De Piccoli
Giacomo
G
Carballo
Jesús A
JA
Cha
Rita S
RS
Jarmuz
Adam
A
Aragón
Luis
L
D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D020090:Chromosome Segregation; D004275:DNA, Ribosomal / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D005785:Gene Conversion / Q000502:physiology; D017353:Gene Deletion; D018628:Gene Dosage; D018816:Genes, cdc; D020459:Genes, rRNA; D008957:Models, Genetic; D009154:Mutation; D009630:Nondisjunction, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000502:physiology*; D015003:Yeasts / Q000166:cytology
D018797:Cell Cycle Proteins; D004275:DNA, Ribosomal; D005656:Fungal Proteins; D012335:RNA, Ribosomal; D012319:RNA Polymerase II