Structural Basis and IP6 Requirement for Pds5-Dependent Cohesin Dynamics.

Structural Basis and IP6 Requirement for Pds5-Dependent Cohesin Dynamics.
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DOI:
10.1016/j.molcel.2016.02.033
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发表时间:
2016-04-21
期刊:
影响因子:
16
通讯作者:
Yu H
Yu H
中科院分区:
生物学1区
文献类型:
--
作者:
Ouyang Z;Zheng G;Tomchick DR;Luo X;Yu H

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环状粘附素复合体通过动态捕获染色体来调节转录、DNA修复和染色体分离,以促进染色体紧凑和姐妹染色单体的凝聚。粘附素环需要打开和关闭,才能将其装载到染色体上并从染色体中释放出来。粘附素的动态受释放因子Pds5和Wap1以及粘附素稳定剂Sororin的控制。在这里,我们报告了人Pds5B的晶体结构,它与Wapl和Sororin中发现的保守多肽基序结合。我们的结构为Wapl和Sororin如何对抗性地影响凝集素动力学奠定了基础。该结构进一步揭示了Pds5能与六磷酸肌醇(IP6)结合。Pds5B的IP6结合片段的形状像钳柄的下巴,它抑制Scc1与Smc3的结合。我们认为,Pds5稳定了一种短暂的、开放的粘附素状态,以促进其从染色体中释放。
The ring-shaped cohesin complex regulates transcription, DNA repair, and chromosome segregation by dynamically entrapping chromosomes to promote chromosome compaction and sister-chromatid cohesion. The cohesin ring needs to open and close to allow its loading to and release from chromosomes. Cohesin dynamics are controlled by the releasing factors Pds5 and Wapl and the cohesin stabilizer Sororin. Here, we report the crystal structure of human Pds5B bound to a conserved peptide motif found in both Wapl and Sororin. Our structure establishes the basis for how Wapl and Sororin antagonistically influence cohesin dynamics. The structure further reveals that Pds5 can bind inositol hexakisphosphate (IP6). The IP6-binding segment of Pds5B is shaped like the jaw of a plier lever and inhibits the binding of Scc1 to Smc3. We propose that Pds5 stabilizes a transient, open state of cohesin to promote its release from chromosomes.
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