Reference: Kaur U, et al. (2025) Autoinhibition imposed by a large conformational switch of INO80 regulates nucleosome positioning. Science 389(6757):eadr3831

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Abstract


Increasing the flanking DNA from 40 to 80 base pairs (bp) causes ~100-fold faster nucleosome sliding by INO80. A prevalent hypothesis posits that the Arp8 module within INO80 enables a ruler-like activity. Using cryogenic electron microscopy, we show that on nucleosomes with 40 bp of flanking DNA, the Arp8 module rotates 180° away from the DNA. Deleting the Arp8 module enables rapid sliding irrespective of flanking DNA length. Thus, rather than enabling a ruler-like activity, the Arp8 module acts as a brake on INO80 remodeling when flanking DNA is short. This autoinhibition-based mechanism has broad implications for understanding how primitive nucleosome mobilization enzymes may have evolved into sophisticated remodelers.

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Journal Article
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Kaur U, Wu H, Cheng Y, Narlikar GJ
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