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Autoinhibitory elements of the Chd1 remodeler block initiation of twist defects by destabilizing the ATPase motor on the nucleosome [Biochemistry]
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2021-01-26 , DOI: 10.1073/pnas.2014498118
Ilana M Nodelman 1 , Zhongtian Shen 1 , Robert F Levendosky 1 , Gregory D Bowman 2
Affiliation  

Chromatin remodelers are ATP (adenosine triphosphate)-powered motors that reposition nucleosomes throughout eukaryotic chromosomes. Remodelers possess autoinhibitory elements that control the direction of nucleosome sliding, but underlying mechanisms of inhibition have been unclear. Here, we show that autoinhibitory elements of the yeast Chd1 remodeler block nucleosome sliding by preventing initiation of twist defects. We show that two autoinhibitory elements—the chromodomains and bridge—reinforce each other to block sliding when the DNA-binding domain is not bound to entry-side DNA. Our data support a model where the chromodomains and bridge target nucleotide-free and ADP-bound states of the ATPase motor, favoring a partially disengaged state of the ATPase motor on the nucleosome. By bypassing distortions of nucleosomal DNA prior to ATP binding, we propose that autoinhibitory elements uncouple the ATP binding/hydrolysis cycle from DNA translocation around the histone core.



中文翻译:

Chd1 重塑剂的自抑制元件通过破坏核小体上的 ATP 酶马达来阻止扭曲缺陷的开始[生物化学]

染色质重塑剂是 ATP(三磷酸腺苷)驱动的马达,可在整个真核染色体中重新定位核小体。Remodelers 拥有控制核小体滑动方向的自抑制元件,但潜在的抑制机制尚不清楚。在这里,我们表明酵母 Chd1 重塑剂的自抑制元件通过阻止扭曲缺陷的启动来阻止核小体滑动。我们表明,当 DNA 结合结构域未与入口侧 DNA 结合时,两种自抑制元件——染色质结构域和桥——相互增强以阻止滑动。我们的数据支持一个模型,其中染色质域和桥接靶向 ATPase 马达的无核苷酸和 ADP 结合状态,有利于核小体上 ATPase 马达的部分脱离状态。通过在 ATP 结合之前绕过核小体 DNA 的扭曲,

更新日期:2021-01-20
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