The Bur1 cyclin-dependent kinase regulates telomere length in Saccharomyces cerevisiae.
The Bur1 cyclin-dependent kinase regulates telomere length in Saccharomyces cerevisiae.
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DOI：
10.1002/yea.3680
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发表时间：
2022-03
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端粒长度调控是真核生物细胞生存所必需的。虽然许多途径影响端粒长度是已知的，我们还没有一个完整的了解长度调节的机制。为了确定可能调节端粒长度的新途径，我们在酵母中进行了遗传筛选，并确定了细胞周期蛋白依赖性激酶复合物Bur 1/2作为端粒长度的调节因子。BUR 1细胞周期蛋白依赖性激酶或相关BUR 2细胞周期蛋白的突变导致端粒变短。这种调节并没有通过已知的BUR 1在调节组蛋白修饰中的作用发挥作用，因为bur 1 BURset 2双突变体挽救了细胞生长，但没有挽救端粒缩短效应。我们发现bur 1 β和bur 2 β set 2 β在从头端粒添加中也有缺陷，并且SET 2的缺失也不能挽救这种延伸缺陷。Bur 1/2细胞周期蛋白依赖性激酶调节许多基因的转录。我们发现，TLC 1 RNA水平降低bur 2 tumset 2 tumset 3突变体，然而，TLC 1的过度表达恢复转录水平，但没有恢复从头端粒延长或端粒长度。这些数据表明，Bur 1/2激酶在端粒延长中起作用，与其在端粒酶组分转录中的作用分开。剖析Bur 1/2激酶通路在端粒中的作用将有助于我们完整地理解端粒长度调控的复杂网络。Bur 1/2是一种细胞周期蛋白依赖性激酶，磷酸化细胞内的许多底物。调节端粒长度平衡的端粒结合复合物通过蛋白质修饰来调节。这种激酶的磷酸化直接或间接调节端粒长度的延长。 Bur 1/2细胞周期蛋白依赖性激酶活性的丧失导致端粒变短。短端粒表型不是由于Bur 1/2在组蛋白修饰中的作用。短端粒不是由于端粒酶组分Est 1，Est 2，Est 3或Tlc 1水平降低所致。在缺乏Bur 1/2活性的情况下，TLC 1缺失的细胞不形成存活细胞。Bur 1/2激酶直接或间接调节端粒长度。
Telomere length regulation is essential for cell viability in eukaryotes. While many pathways that affect telomere length are known, we do not yet have a complete understanding of the mechanism of length regulation. To identify new pathways that might regulate telomere length, we carried out a genetic screen in yeast and identified the cyclin‐dependent kinase complex Bur1/2 as a regulator of telomere length. Mutations in either BUR1 cyclin‐dependent kinase or the associated BUR2 cyclin resulted in short telomeres. This regulation did not function through the known role of BUR1 in regulating histone modification as bur1∆ set2∆ and bur2∆ set2∆ double mutants rescued cell growth but did not rescue the telomere shortening effects. We found that both bur1∆ and bur2∆ set2∆ were also defective in de novo telomere addition, and deletion of SET2 did also not rescue this elongation defect. The Bur1/2 cyclin‐dependent kinase regulates transcription of many genes. We found that TLC1 RNA levels were reduced in bur2∆ set2∆ mutants; however, overexpression of TLC1 restored the transcript levels but did not restore de novo telomere elongation or telomere length. These data suggest that the Bur1/2 kinase plays a role in telomere elongation separate from its role in transcription of telomerase components. Dissecting the role of the Bur1/2 kinase pathway at telomeres will help complete our understanding of the complex network of telomere length regulation. Bur1/2 is a cyclin‐dependent kinase that phosphorylates many substrates within the cell. Telomere binding complexes regulating telomere length equilibrium are regulated through protein modification. Phosphorylation by this kinase either directly or indirectly regulates telomere length elongation. Loss of Bur1/2 cyclin‐dependent kinase activity causes short telomeres. Short telomere phenotype is not due to the role of Bur1/2 in histone modification. Short telomeres are not due to decreased levels of telomerase components Est1, Est2, Est3, or Tlc1. In absence of Bur1/2 activity, TLC1 deleted cells do not form survivors. Bur1/2 kinase directly or indirectly regulates telomere length.