A domain of Rad9 specifically required for activation of Chk1 in budding yeast
A domain of Rad9 specifically required for activation of Chk1 in budding yeast
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DOI：
10.1242/jcs.00907
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发表时间：
2004-02-01
影响因子：
4
通讯作者：
Lydall, D
中科院分区：
文献类型：
--
作者：
Blankley, RT;Lydall, D
Rad 9蛋白是酿酒酵母DNA损伤检查点途径中的关键衔接蛋白。其衔接子功能是将Mec 1激酶的活性与依赖于Rad 53和Chk 1激酶的两个平行信号通路的激活联系起来。Rad 9与Rad 53相互作用并激活Rad 53的机制已经很好地理解。然而，很少有人知道Rad 9如何促进Chk 1的激活。我们在这里表明，Rad 9的N-末端是特别重要的磷酸化和激活的Chk 1激酶，但不是Rad 53激酶的磷酸化和激活。Rad 9的Chk 1激活结构域（CAD）对于cdc 13 -1和yku 70 Delta诱导的端粒损伤后的信号细胞周期停滞特别重要，但对于耐受紫外线诱导的损伤或抑制端粒处的核酸酶活性不重要。这项工作扩展了数据，表明Rad 9衔接蛋白内的可分离结构域允许其独立地激活两个不同的激酶信号通路。
The Rad9 protein is a key adaptor protein in Saccharomyces cerevisiae DNA damage checkpoint pathways. Its adaptor function is to link the activity of the Mec1 kinase to the activation of two parallel signalling pathways dependent on the Rad53 and Chk1 kinases. The mechanisms by which Rad9 interacts with, and activates, Rad53 are well understood. However, little was known about how Rad9 facilitates the activation of Chk1. We show here that the N-terminus of Rad9 is specifically important for phosphorylation and activation of the Chk1 kinase but not for the phosphorylation and activation of the Rad53 kinase. The Chk1 activation domain (CAD) of Rad9 is specifically important for signalling cell-cycle arrest after cdc13-1- and yku70Delta-induced telomere damage but not for tolerating ultraviolet-induced damage or inhibiting nuclease activity at telomeres. This work extends data showing that separable domains within the Rad9 adaptor protein allow it to activate two distinct kinase signalling pathways independently of each other.