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Dss1 release activates DNA binding potential in Brh2

机译:Dss1释放激活Brh2中的DNA结合潜力

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摘要

Dss1 is an intrinsically unstructured polypeptide that partners with the much larger Brh2 protein, the BRCA2 ortholog in Ustilago maydis, to form a tight complex. Mutants lacking Dss1 have essentially the same phenotype as mutants defective in Brh2, implying that through physical interaction Dss1 serves as a positive activator of Brh2. Dss1 associates with Brh2 through an interaction surface in the carboxy-terminal region. Certain derivatives of Brh2 lacking this interaction surface remain highly competent in DNA repair as long as a DNA-binding domain is present. However, the Dss1-independent activity raises the question of what function might be met in the native protein by having Brh2 under Dss1 control. Using a set of Brh2 fusions and truncated derivatives, we show here that Dss1 is capable of exerting control when there is a cognate Dss1-interacting surface present. We find that association of Dss1 attenuates the DNA binding potential of Brh2 and that the amino-terminal domain of Brh2 helps evict Dss1 from its carboxy-terminal interaction surface. The findings presented here add to the notion that Dss1 serves in a regulatory capacity to dictate order in association of Brh2's amino-terminal and carboxy-terminal domains with DNA.
机译:Dss1是一种固有的非结构化多肽,可与更大的Brh2蛋白(Ustilago maydis中的BRCA2 ortholog)结合形成紧密的复合物。缺少Dss1的突变体具有与Brh2缺陷型突变体基本相同的表型,这意味着通过物理相互作用Dss1可以作为Brh2的阳性激活剂。 Dss1通过羧基末端区域中的相互作用表面与Brh2缔合。只要存在DNA结合结构域,某些缺少此相互作用表面的Brh2衍生物仍具有很高的DNA修复能力。但是,不依赖于Dss1的活性提出了一个问题,即通过将Brh2置于Dss1的控制之下,天然蛋白可能具有什么功能。使用一组Brh2融合和截短的导数,我们在这里显示Dss1能够在存在相关的Dss1相互作用表面时发挥控制作用。我们发现,Dss1的关联减弱了Brh2的DNA结合潜力,并且Brh2的氨基末端结构域有助于从其羧基末端相互作用表面驱逐Dss1。此处提出的发现增加了Dss1以调节能力来指示Brh2的氨基末端和羧基末端结构域与DNA关联的顺序的概念。

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