INO80 Chromatin Remodeler Facilitates Release of RNA Polymerase II from Chromatin for Ubiquitin-Mediated Proteasomal Degradation.
INO80 Chromatin Remodeler Facilitates Release of RNA Polymerase II from Chromatin for Ubiquitin-Mediated Proteasomal Degradation.
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INO80 染色质重塑器促进 RNA 聚合酶 II 从染色质中释放，以实现泛素介导的蛋白酶体降解。
DOI：
10.1016/j.molcel.2015.10.028
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发表时间：
2015-12-03
期刊：
影响因子：
16
通讯作者：
Papamichos-Chronakis M
中科院分区：
文献类型：
--
作者：
Lafon A;Taranum S;Pietrocola F;Dingli F;Loew D;Brahma S;Bartholomew B;Papamichos-Chronakis M
转录应激过程中，RNA 聚合酶 II (RNAPII) 在染色质上的停滞会导致 RNAPII 最大亚基 Rpb1 被泛素蛋白酶体系统 (UPS) 多泛素化和降解。在这里，我们报道了酵母中染色质结合 RNAPII 的周转需要 ATP 依赖性染色质重塑复合物 INO80。 INO80 在物理和功能上与 Cdc48/p97/VCP 相互作用，Cdc48/p97/VCP 是 RNAPII 降解所需的 UPS 组件。缺乏 INO80 的细胞在 Rpb1 降解方面存在缺陷，并在染色质上积累紧密结合的泛素化 Rpb1。 INO80 与 RNAPII 和 Cdc48 形成三元复合物，并以准备降解的 Rpb1 为目标。 INO80 在 RNAPII 周转中的功能是基因毒性应激期间细胞生长和存活所必需的。我们的结果确定 INO80 是 RNAPII 降解蛋白水解途径的真正组成部分，并表明 INO80 核小体重塑活性促进泛素化 Rpb1 从染色质解离，以保护基因组的完整性。
Stalling of RNA Polymerase II (RNAPII) on chromatin during transcriptional stress results in polyubiquitination and degradation of the largest subunit of RNAPII, Rpb1, by the ubiquitin proteasome system (UPS). Here, we report that the ATP-dependent chromatin remodeling complex INO80 is required for turnover of chromatin-bound RNAPII in yeast. INO80 interacts physically and functionally with Cdc48/p97/VCP, a component of UPS required for degradation of RNAPII. Cells lacking INO80 are defective in Rpb1 degradation and accumulate tightly bound ubiquitinated Rpb1 on chromatin. INO80 forms a ternary complex with RNAPII and Cdc48 and targets Rpb1 primed for degradation. The function of INO80 in RNAPII turnover is required for cell growth and survival during genotoxic stress. Our results identify INO80 as a bona fide component of the proteolytic pathway for RNAPII degradation and suggest that INO80 nucleosome remodeling activity promotes the dissociation of ubiquitinated Rpb1 from chromatin to protect the integrity of the genome.