Regulation of telomere elongation by the cyclin-dependent kinase CDK1
Regulation of telomere elongation by the cyclin-dependent kinase CDK1
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DOI：
10.1016/j.molcel.2006.10.020
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发表时间：
2006-11-03
期刊：
影响因子：
16
通讯作者：
Greider, Carol W.
中科院分区：
文献类型：
--
作者：
Frank, Christopher J.;Hyde, Molly;Greider, Carol W.
端粒延长是细胞周期调控的，需要参与DNA损伤反应的蛋白质的协调活性。我们使用了一种检测从头端粒除了检查细胞周期蛋白依赖性激酶Cdk1（Cdc28）在细胞周期特异性端粒延长的作用。抑制ATP类似物敏感的等位基因Cdk1完全阻断了端粒重复序列的添加。Rif2和DNA聚合酶α的突变导致端粒延长增加，但不能补偿Cdk1活性的损失，这表明Cdk1活性是端粒增加的早期步骤所必需的。在双链断裂处与Cdk1起作用的DNA修复蛋白的突变也阻止了端粒的伸长。Cdk1活性是在天然和从头端粒处产生3'单链突出端所必需的。我们建议Cdk1活性控制端粒延长的时间，通过调节染色体末端的单链突出。
Telomere elongation is cell-cycle regulated and requires the coordinated activity of proteins involved in the DNA damage response. We used an assay that detects de novo telomere addition to examine the role of the cyclin-dependent kinase Cdk1 (Cdc28) in cell-cycle-specific telomere elongation. Inhibition of an ATP analog-sensitive allele of Cdk1 completely blocked the addition of telomere repeats. Mutations in Rif2 and DNA polymerase alpha that cause increased telomere elongation were unable to compensate for the loss of Cdk1 activity, suggesting Cdk1 activity is required for an early step in telomere addition. Mutations in DNA repair proteins that act with Cdk1 at double-strand breaks also prevented telomere elongation. Cdk1 activity was required for the generation of 3' single-strand overhangs at both native and de novo telomeres. We propose Cdk1 activity controls the timing of telomere elongation by regulating the single-strand overhang at chromosome ends.