Deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains. Shows only weak activity against 'Lys-11' and 'Lys-48'-linked chains (PubMed:29576528, PubMed:29563501, PubMed:29476094). Plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage (PubMed:29576528, PubMed:29576527). Modulates the ubiquitination status of replication protein A (RPA) complex proteins in response to replication stress (PubMed:29563501). Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). kcat is 4.9 sec(-1) with Arg-Leu-Arg-Gly-Gly-AMC as substrate (PubMed:29476094). kcat is 0.084 sec(-1) with Ub-Rhodamine as substrate (PubMed:29576528). Interacts with RPA1 and RPA2. Mostly present in the nuclear fraction. Localizes to DNA lesions. The motif interacting with ubiquitin (MIU) and ZUFSP ubiquitin-binding domain (zUBD, also called ZUFSP helical arm ZHA) are responsible for binding the distal (outgoing) ubiquitin units S1 and S2 respectively. C2H2-type zinc finger 4 is a ubiquitin-binding zinc finger (UBZ) and required for polyubiquitin binding, possibly binding the proximal ubiqutin, and for catalytic activity (PubMed:29576528) (Probable). C2H2-type zinc fingers 1-3 are required for localization to sites of DNA damage (PubMed:29576528). Belongs to the peptidase C78 family. ZUFSP subfamily.