Torres-Rosell Jordi, De Piccoli Giacomo, Cordon-Preciado Violeta, Farmer Sarah, Jarmuz Adam, Machin Felix, Pasero Philippe, Lisby Michael, Haber James E, Aragón Luis
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.
Science. 2007 Mar 9;315(5817):1411-5. doi: 10.1126/science.1134025.
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.
细胞周期检查点可在复制叉停滞时阻止有丝分裂。检查点是否也能确保在有丝分裂之前完成DNA复制尚不清楚。在这里，我们表明，在与黏连蛋白和凝聚素相关的酵母smc5-smc6突变体中，复制会延迟，在核糖体DNA基因簇等天然阻碍复制的位点最为显著。在缺乏Smc5-Smc6的情况下，尽管检查点反应完整，但由于有丝分裂进入时复制未完成，会发生染色体不分离。消除阻碍复制叉进展的过程可恢复smc5-smc6突变体中复制与分离之间的时间解偶联。我们提出，复制的完成不受已知检查点的监测。
