Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast
Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast
复制标题
DOI：
10.1038/emboj.2011.404
复制
发表时间：
2011-11-30
期刊：
影响因子：
11.4
通讯作者：
Zegerman, Philip
中科院分区：
文献类型：
--
作者：
Mantiero, Davide;Mackenzie, Amanda;Zegerman, Philip
真核染色体从多个来源复制，在细胞周期的整个S期开始。为什么所有的起点不同时发射在S-阶段的开始是未知的，但两个激酶的活动，细胞周期蛋白依赖性激酶（CDK）和Dbf 4依赖性激酶（DDK），是不断需要在整个S-阶段的所有复制起始事件。在这里，我们表明，两个CDK底物Sld 3和Sld 2和它们的结合伙伴Dpb 11，连同DDK亚基Dbf 4是在低丰度的芽殖酵母，酿酒酵母。这些因子的过表达足以使晚期发射的复制起点早期启动，并与组蛋白脱乙酰酶RPD 3的缺失一起促进异染色质的休眠起点的发射。我们表明，正常的程序的起源射击防止不适当的检查点激活和控制S-期长度在芽殖酵母。这些结果解释了如何限制DDK激酶和CDK的目标在起点的竞争调节复制起始动力学在S期，并建立了一个独特的系统，调查的生物学作用的时间程序的起源射击。The EMBO Journal（2011）30，4805-4814. doi：10.1038/doj.2011.404; 2011年11月11日在线发布
Eukaryotic chromosomes are replicated from multiple origins that initiate throughout the S-phase of the cell cycle. Why all origins do not fire simultaneously at the beginning of S-phase is not known, but two kinase activities, cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK), are continually required throughout the S-phase for all replication initiation events. Here, we show that the two CDK substrates Sld3 and Sld2 and their binding partner Dpb11, together with the DDK subunit Dbf4 are in low abundance in the budding yeast, Saccharomyces cerevisiae. Over-expression of these factors is sufficient to allow late firing origins of replication to initiate early and together with deletion of the histone deacetylase RPD3, promotes the firing of heterochromatic, dormant origins. We demonstrate that the normal programme of origin firing prevents inappropriate checkpoint activation and controls S-phase length in budding yeast. These results explain how the competition for limiting DDK kinase and CDK targets at origins regulates replication initiation kinetics during S-phase and establishes a unique system with which to investigate the biological roles of the temporal programme of origin firing. The EMBO Journal (2011) 30, 4805-4814. doi:10.1038/emboj.2011.404; Published online 11 November 2011