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Anaphase Onset Before Complete DNA Replication with Intact Checkpoint Responses
Jordi Torres-Rosell,1*Giacomo De Piccoli,1*Violeta Cordon-Preciado,1Sarah Farmer,1Adam Jarmuz,1Felix Machin,1Philippe Pasero,2Michael Lisby,3James E. Haber,4Luis Aragón1
Cellular checkpoints prevent mitosis in the presence of stalledreplication forks. Whether checkpoints also ensure the completionof DNA replication before mitosis is unknown. Here, we showthat in yeast smc5-smc6 mutants, which are related to cohesinand condensin, replication is delayed, most significantly atnatural replication-impeding loci like the ribosomal DNA genecluster. In the absence of Smc5-Smc6, chromosome nondisjunctionoccurs as a consequence of mitotic entry with unfinished replicationdespite intact checkpoint responses. Eliminating processes thatobstruct replication fork progression restores the temporaluncoupling between replication and segregation in smc5-smc6mutants. We propose that the completion of replication is notunder the surveillance of known checkpoints.
1 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. 2 Institute of Human Genetics, CNRS Unité Propre de Recherche 1142, 141 Rue de la Cardonille, 34396 Montpellier, France. 3 Department of Genetics, Institute of Molecular Biology and Physiology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353 Copenhagen, Denmark. 4 Rosenstiel Center, Brandeis University, 415 South Street, Mail Stop 029, Waltham, MA 024549110, USA.
* These authors contributed equally to this work.
Present address: Departament Ciències MèdiquesBàsiques, Facultat de Medicina, Universitat de Lleida,Montserrat Roig 2, 25008 Lleida, Spain.
Present address: Unidad de Investigación, Hospital UniversitarioNuestra Señora de Candelaria, Carretera del Rosario sinnúmero, 38010, Santa Cruz de Tenerife, Spain.
To whom correspondence should be addressed. E-mail: luis.aragon{at}csc.mrc.ac.uk
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