The yeast S phase checkpoint enables replicating chromosomes to bi-orient and restrain spindle extension during S phase distress
The yeast S phase checkpoint enables replicating chromosomes to bi-orient and restrain spindle extension during S phase distress
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DOI：
10.1083/jcb.200412076
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发表时间：
2005-03-28
影响因子：
7.8
通讯作者：
Fielding, CS
中科院分区：
文献类型：
--
作者：
Bachant, J;Jessen, SR;Fielding, CS
芽殖酵母S期检查点通过防止复制叉崩溃和未复制染色体的分离来响应于羟基脲诱导的核苷酸耗尽。虽然块染色体分离已被认为是通过抑制后期发生，我们发现检查点缺陷的rad 53突变体经历了周期的纺锤体延伸和崩溃后，羟基脲处理，是不同的后期细胞。此外，染色单体凝聚，其溶解触发后期，是S期检查点阻滞。着丝粒-纺锤体附件是T所需的，以防止在复制块期间纺锤体延伸，并且具有两个着丝粒或与一个着丝粒并列的复制起点的染色体挽救了rad 53检查点缺陷。这些观察结果表明，检查点信号需要产生一个向内的力量参与维持前期纺锤体的完整性在DNA复制窘迫。我们建议，在这些条件下，通过促进复制叉的完整性，Rad 53确保着丝粒复制。然后，复制染色体可以以不依赖于粘着蛋白的方式双向定向，以抑制不合时宜的纺锤体延伸。
The budding yeast S phase checkpoint responds to hydroxyurea-induced nucleotide depletion by preventing replication fork collapse and the segregation of unreplicated chromosomes. Although the block to chromosome segregation has been thought to occur by inhibiting anaphase, we show checkpoint-defective rad53 mutants undergo cycles of spindle extension and collapse after hydroxyurea treatment that are distinct from anaphase cells. Furthermore, chromatid cohesion, whose dissolution triggers anaphase, is dispensable for S phase checkpoint arrest. Kinetochore-spindle attachments are T required to prevent spindle extension during replication blocks, and chromosomes with two centromeres or an origin of replication juxtaposed to a centromere rescue the rad53 checkpoint defect. These observations suggest that checkpoint signaling is required to generate an inward force involved in maintaining preanaphase spindle integrity during DNA replication distress. We propose that by promoting replication fork integrity under these conditions Rad53 ensures centromere duplication. Replicating chromosomes can then bi-orient in a cohesin-independent manner to restrain untimely spindle extension.