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Science 9 March 2007:
Vol. 315. no. 5817, pp. 1411 - 1415
DOI: 10.1126/science.1134025
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Reports

Anaphase Onset Before Complete DNA Replication with Intact Checkpoint Responses

Jordi Torres-Rosell,1*{dagger} Giacomo De Piccoli,1* Violeta Cordon-Preciado,1 Sarah Farmer,1 Adam Jarmuz,1 Felix Machin,1{ddagger} Philippe Pasero,2 Michael Lisby,3 James E. Haber,4 Luis Aragón1§

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.

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 02454–9110, USA.

* These authors contributed equally to this work.

{dagger} Present address: Departament Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, Montserrat Roig 2, 25008 Lleida, Spain.

{ddagger} Present address: Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Carretera del Rosario sin número, 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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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Genetic Screen for Increased Loss of Heterozygosity in Saccharomyces cerevisiae.
M. P. Andersen, Z. W. Nelson, E. D. Hetrick, and D. E. Gottschling (2008)
Genetics 179, 1179-1195
   Abstract »    Full Text »    PDF »
Regulation of Rtt107 Recruitment to Stalled DNA Replication Forks by the Cullin Rtt101 and the Rtt109 Acetyltransferase.
T. M. Roberts, I. W. Zaidi, J. A. Vaisica, M. Peter, and G. W. Brown (2008)
Mol. Biol. Cell 19, 171-180
   Abstract »    Full Text »    PDF »
Hey, I'm still replicating!.
R. Williams (2007)
J. Cell Biol. 177, 4
   Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)