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在 B 型细胞周期蛋白中,只有 CLB5 和 CLB6 能够促进酿酒酵母的减数分裂前 S 期。

Among B-type cyclins only CLB5 and CLB6 promote premeiotic S phase in Saccharomyces cerevisiae.

机构信息

Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.

出版信息

Genetics. 2012 Mar;190(3):1001-16. doi: 10.1534/genetics.111.134684. Epub 2011 Dec 29.

Abstract

The Saccharomyces cerevisiae cyclin Clb5 is required for premeiotic S phase, meiotic recombination, and successful progression through meiosis. Clb5 is not essential for mitotic proliferation because Clb1-Clb4 can support DNA replication in clb5 clb6 mutants. Clb1, Clb3, and Clb4 accumulate in clb5 clb6 cells during meiotic differentiation yet fail to promote premeiotic DNA replication. When expressed under the regulation of the CLB5 promoter, Clb1 and Clb3 accumulate and are active in the early stages of meiotic differentiation but cannot induce premeiotic DNA replication, suggesting that they do not target Cdk1 to the necessary substrates. The Clb5 hydrophobic patch (HP) residues are important for Clb5 function but this motif alone does not provide the specificity required for Clb5 to induce premeiotic S phase. Domain exchange experiments demonstrated that the amino terminus of Clb5 when fused to Clb3 confers upon Clb3 the ability to induce premeiotic S phase. Chimeric cyclins containing smaller regions of the Clb5 amino terminus displayed reduced ability to activate premeiotic DNA replication despite being more abundant and having greater associated histone H1 kinase activity than endogenous Clb5. These observations suggest that Clb5 has a unique ability to trigger premeiotic S phase and that the amino-terminal region of Clb5 contributes to its specificity and regulates the functions performed by the cyclin-Cdk complex.

摘要

酿酒酵母细胞周期蛋白 Clb5 是减数前期 S 期、减数重组和成功通过减数分裂所必需的。Clb5 对于有丝分裂增殖不是必需的,因为 Clb1-Clb4 可以支持 clb5 clb6 突变体中的 DNA 复制。Clb1、Clb3 和 Clb4 在减数分裂分化过程中在 clb5 clb6 细胞中积累,但不能促进减数前期 DNA 复制。当在 CLB5 启动子的调控下表达时,Clb1 和 Clb3 在减数分裂分化的早期积累并具有活性,但不能诱导减数前期 DNA 复制,表明它们不会将 Cdk1 靶向必要的底物。Clb5 的疏水性斑块 (HP) 残基对 Clb5 功能很重要,但该基序本身并不能提供 Clb5 诱导减数前期 S 期所需的特异性。结构域交换实验表明,Clb5 的氨基末端与 Clb3 融合赋予 Clb3 诱导减数前期 S 期的能力。含有 Clb5 氨基末端较小区域的嵌合细胞周期蛋白尽管比内源性 Clb5 更丰富且具有更大的相关组蛋白 H1 激酶活性,但激活减数前期 DNA 复制的能力降低。这些观察结果表明,Clb5 具有独特的能力来触发减数前期 S 期,并且 Clb5 的氨基末端区域有助于其特异性并调节细胞周期蛋白-Cdk 复合物执行的功能。

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