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bioRxiv · 10.1101/2024.05.10.593625

Conformational switching of Arp5 subunit differentially regulates INO80 chromatin remodeling

Bartholomew, B.·Garcia, J.·Paul, S.·Shukla, S.·Zhong, Y.·Beauchemin, K.
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Abstract

The INO80 chromatin remodeler is a versatile enzyme capable of several functions, including spacing nucleosomes equal distances apart, precise positioning of nucleosomes based on DNA shape/sequence and exchanging histone dimers. Within INO80, the Arp5 subunit plays a central role in INO80 remodeling, evidenced by its interactions with the histone octamer, nucleosomal and extranucleosomal DNA, and its necessity in linking INO80s ATPase activity to nucleosome movement. Our investigation reveals that the grappler domain of Arp5 interacts with the acidic pocket of nucleosomes through two distinct mechanisms: an arginine anchor or a hydrophobic/acidic patch. These two modes of binding serve distinct functions within INO80 as shown in vivo by mutations in these regions resulting in varying phenotypes and in vitro by diverse effects on nucleosome mobilization. Our findings suggest that the hydrophobic/acidic patch of Arp5 is likely important for dimer exchange by INO80, while the arginine anchor is crucial for mobilizing nucleosomes.

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Bartholomew, B., Garcia, J., Paul, S., Shukla, S., Zhong, Y., Beauchemin, K.. 2024-05-11. Conformational switching of Arp5 subunit differentially regulates INO80 chromatin remodeling. https://doi.org/10.1101/2024.05.10.593625

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