Ubiquitin‐associated (UBA) domains in Rad23 bind ubiquitin and promote inhibition of multi‐ubiquitin chain assembly

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Abstract
Rad23 is a DNA repair protein that promotes the assembly of the nucleotide excision repair complex. Rad23 can interact with the 26S proteasome through an N‐terminal ubiquitin‐like domain, and inhibits the assembly of substrate‐linked multi‐ubiquitin (multi‐Ub) chains in vitro and in vivo . Significantly, Rad23 can bind a proteolytic substrate that is conjugated to a few ubiquitin (Ub) moieties. We report here that two ubiquitin‐associated (UBA) domains in Rad23 form non‐covalent interactions with Ub. A mutant that lacked either UBA sequence was capable of blocking the assembly of substrate‐linked multi‐Ub chains, although a mutant that lacked both UBA domains was significantly impaired. These studies suggest that the interaction with Ub is required for Rad23 activity, and that other UBA‐containing proteins may have a similar function.