Condensin-dependent rDNA decatenation introduces a temporal pattern to chromosome segregation
Condensin-dependent rDNA decatenation introduces a temporal pattern to chromosome segregation
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DOI：
10.1016/j.cub.2008.06.058
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发表时间：
2008-07-22
期刊：
影响因子：
9.2
通讯作者：
Uhlmann, Frank
中科院分区：
文献类型：
--
作者：
D'Ambrosio, Claudio;Kelly, Gavin;Uhlmann, Frank
染色体凝聚素复合体赋予中期染色体结构稳定性。此外，在分裂后期姐妹染色单体分离过程中，姐妹染色单体的分离需要凝聚素[1-7]。凝聚素如何促进染色体的分辨率知之甚少。后期的染色体分离在拓扑异构酶II（topo II）失活后也失败了，拓扑异构酶II是一种酶，可以去除DNA复制完成后留下的姐妹染色单体之间的连锁[8，9]。这导致了浓缩蛋白促进DNA解链的提议[3，10，II]，但这一点的直接证据缺失，并且已经提出了浓缩蛋白在染色体解析中的替代作用[12-14]。使用芽殖酵母rDNA作为一个模型，我们现在表明，后期桥梁在凝聚素突变体解决异位表达的外来（小球藻病毒），但不是内源性拓扑异构酶II。这表明，连锁防止姐妹rDNA分离，但酵母拓扑酶II是无效的decatenating没有凝聚酶的基因座。凝聚蛋白和拓扑异构酶II共定位沿着rDNA和常染色质，与它们的活动协调一致。我们研究了凝聚素依赖的rDNA脱连锁的生理后果，发现后期脱连锁决定了后期分离的时间。因此，去连环化的调节提供了一种微调有丝分裂中染色体分离时间的手段。
The chromosomal condensin complex gives metaphase chromosomes structural stability. In addition, condensin is required for sister-chromatid resolution during their segregation in anaphase [1-7]. How condensin promotes chromosome resolution is poorly understood. Chromosome segregation during anaphase also fails after inactivation of topoisomerase II (topo II), the enzyme that removes catenation between sister chromatids left behind after completion of DNA replication [8, 9]. This has led to the proposal that condensin promotes DNA decatenation [3, 10, II], but direct evidence for this is missing and alternative roles for condensin in chromosome resolution have been suggested [12-14]. Using the budding-yeast rDNA as a model, we now show that anaphase bridges in a condensin mutant are resolved by ectopic expression of a foreign (Chlorella virus) but not endogenous topo II. This suggests that catenation prevents sister-rDNA segregation but that,yeast topo II is ineffective in decatenating the locus without condensin. Condensin and topo II colocalize along both rDNA and euchromatin, consistent with coordination of their activities. We investigate the physiological consequences of condensin-dependent rDNA decatenation and find that late decatenation determines the late segregation timing of this locus during anaphase. Regulation of decatenation therefore provides a means to fine tune the segregation timing of chromosomes in mitosis.