Anaphase onset before complete DNA replication with intact checkpoint responses |
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| Authors: | Torres-Rosell Jordi De Piccoli Giacomo Cordon-Preciado Violeta Farmer Sarah Jarmuz Adam Machin Felix Pasero Philippe Lisby Michael Haber James E Aragón Luis |
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| Institution: | 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. |
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| Abstract: | 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. |
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