Pol12 the B subunit of DNA polymerase α, functions in both telomere capping and length regulation
Pol12 the B subunit of DNA polymerase α, functions in both telomere capping and length regulation
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DOI：
10.1101/gad.300004
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发表时间：
2004-05-01
影响因子：
10.5
通讯作者：
Shore, D
中科院分区：
文献类型：
--
作者：
Grossi, S;Puglisi, A;Shore, D
端粒酶作用的调节，以及它与常规DNA复制和染色体末端“加帽”的协调，仍然知之甚少。在这里，我们描述了一个基因筛选在酵母中的突变体与放松端粒长度调节，并确定Pol 12，B亚基的DNA聚合酶α（Pol 1）-引发酶复合物，作为一个新的因素参与这一过程。与许多POL 1和POL 12突变不同，它们也会导致端粒延长，这里描述的pol 12 -216突变不会导致Poll功能降低，端粒单链DNA增加或端粒基因沉默减少。相反，与影响POL 1的突变不同，pol 12 -216与端粒末端结合和加帽蛋白Stn 1中的突变组合是致命的。值得注意的是，Pol 12和Stn 1在双杂交和生物化学测定中相互作用，并且它们的合成致死相互作用似乎至少部分是由端粒帽的损失引起的。这些数据揭示了Pol 12的新功能以及DNA聚合酶α和Stn 1之间的新联系。我们建议Pol 12，与Stn 1一起，在连接端粒酶作用与滞后链合成的完成中起着关键作用，并且在端粒加帽所需的调节步骤中起着关键作用。
The regulation of telomerase action, and its coordination with conventional DNA replication and chromosome end "capping," are still poorly understood. Here we describe a genetic screen in yeast for mutants with relaxed telomere length regulation, and the identification of Pol12, the B subunit of the DNA polymerase alpha (Pol1)-primase complex, as a new factor involved in this process. Unlike many POL1 and POL12 mutations, which also cause telomere elongation, the pol12-216 mutation described here does not lead to either reduced Poll function, increased telomeric single-stranded DNA, or a reduction in telomeric gene silencing. Instead, and again unlike mutations affecting POL1, pol12-216 is lethal in combination with a mutation in the telomere end-binding and capping protein Stn1. Significantly, Pol12 and Stn1 interact in both two-hybrid and biochemical assays, and their synthetic-lethal interaction appears to be caused, at least in part, by a loss of telomere capping. These data reveal a novel function for Pol12 and a new connection between DNA polymerase alpha and Stn1. We propose that Pol12, together with Stn1, plays a key role in linking telomerase action with the completion of lagging strand synthesis, and in a regulatory step required for telomere capping.