Anaphase onset before complete DNA replication with intact checkpoint responses.
Cellular checkpoints prevent mitosis in the presence of stalled replication forks. Whether checkpoints also ensure the completion of DNA replication before mitosis is unknown. Here, we show that in yeast smc5-smc6 mutants, which are related to cohesin and condensin, replication is delayed, most significantly at natural replication-impeding loci like the ribosomal DNA gene cluster. In the absence of Smc5-Smc6, chromosome nondisjunction occurs as a consequence of mitotic entry with unfinished replication despite intact checkpoint responses. Eliminating processes that obstruct replication fork progression restores the temporal uncoupling between replication and segregation in smc5-smc6 mutants. We propose that the completion of replication is not under the surveillance of known checkpoints.
Torres-Rosell
Jordi
J
Cell Cycle Group, Medical Research Council (MRC) Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
De Piccoli
Giacomo
G
Cordon-Preciado
Violeta
V
Farmer
Sarah
S
Jarmuz
Adam
A
Machin
Felix
F
Pasero
Philippe
P
Lisby
Michael
M
Haber
James E
JE
Aragón
Luis
L
D000705:Anaphase; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D064447:Checkpoint Kinase 2; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D005800:Genes, Fungal; D020459:Genes, rRNA; D008677:Metaphase; D008938:Mitosis; D008957:Models, Genetic; D009154:Mutation; D009630:Nondisjunction, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004275:DNA, Ribosomal; C486627:SMC5 protein, S cerevisiae; C486631:SMC6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae