酵母 INO80 复合物作为一个可调 DNA 长度敏感性开关来调节核小体滑动。
The Yeast INO80 Complex Operates as a Tunable DNA Length-Sensitive Switch to Regulate Nucleosome Sliding.
机构信息
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
出版信息
Mol Cell. 2018 Feb 15;69(4):677-688.e9. doi: 10.1016/j.molcel.2018.01.028.
The yeast INO80 chromatin remodeling complex plays essential roles in regulating DNA damage repair, replication, and promoter architecture. INO80's role in these processes is likely related to its ability to slide nucleosomes, but the underlying mechanism is poorly understood. Here we use ensemble and single-molecule enzymology to study INO80-catalyzed nucleosome sliding. We find that the rate of nucleosome sliding by INO80 increases ∼100-fold when the flanking DNA length is increased from 40 to 60 bp. Furthermore, once sliding is initiated, INO80 moves the nucleosome rapidly at least 20 bp without pausing to re-assess flanking DNA length, and it can change the direction of nucleosome sliding without dissociation. Finally, we show that the Nhp10 module of INO80 plays an auto-inhibitory role, tuning INO80's switch-like response to flanking DNA. Our results indicate that INO80 is a highly processive remodeling motor that is tightly regulated by both substrate cues and non-catalytic subunits.
酵母 INO80 染色质重塑复合物在调节 DNA 损伤修复、复制和启动子结构方面发挥着重要作用。INO80 在这些过程中的作用可能与其滑动核小体的能力有关，但潜在的机制知之甚少。在这里，我们使用整体和单分子酶学研究 INO80 催化的核小体滑动。我们发现，当侧翼 DNA 长度从 40 增加到 60bp 时，INO80 介导的核小体滑动速率增加了约 100 倍。此外，一旦滑动被启动，INO80 至少在 20bp 内快速移动核小体，而不会暂停重新评估侧翼 DNA 长度，并且它可以在不解离的情况下改变核小体滑动的方向。最后，我们表明 INO80 的 Nhp10 模块发挥自动抑制作用，调节 INO80 对侧翼 DNA 的开关样反应。我们的结果表明，INO80 是一种高度连续的重塑马达，受到底物线索和非催化亚基的严格调控。
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