Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability

• DOI: 10.1016/j.molcel.2018.02.023
• Publication Date: 2018-03-22T15:51:32Z
• Authors: Dominika Kwasna; Syed Arif Abdul R...; Jayaprakash Natar...; Stephen Matthews; Ross Madden; Virginia De Cesare; Simone Weidlich; Satpal Virdee; Ivan Ahel; Ian Gibbs-Seymour; Yogesh Kulathu
• Keywords: Deubiquitinating enzyme; Cleave; Ubiquitins

Deubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling. Here, we report the discovery deubiquitinating activity in ZUFSP/C6orf113. High-resolution crystal structures ZUFSP complex with reveal several distinctive features recognition and catalysis. Our analyses that is a novel DUB no homology to any known DUBs, leading us classify as seventh family. Intriguingly, minimal catalytic domain does not cleave polyubiquitin. We identify two binding domains ZUFSP: ZHA (ZUFSP helical arm) binds distal an atypical UBZ Importantly, both essential for selectively K63-linked show localizes DNA lesions, where it plays role genome stability pathways, functioning prevent spontaneous damage also promote cellular survival response exogenous damage.