Metalloendopeptidase that acts selectively on DNA-binding proteins. DNA is needed to bring the protease and substrates together to enable proteolysis. Involved in the repair of toxic DNA-protein cross-links (DPCs) such as covalently trapped topoisomerase 1 (TOP1) adducts on DNA lesions or DPCs induced by reactive compounds such as formaldehyde. Involved in DNA damage response and processing of stalled or collapsed replication forks by removing the covalently trapped TOP1 from chromatin. DPC proteolysis enables the repair of the lesions via downstream DNA repair pathways. May be recruited to DPCs via the SUMOylation of substrate proteins at damaged DNA sites. Inactivated by EDTA. Binds to DNA. Interacts with CDC48 and SMT3. Interacts with PSY2 and TOF1. Present in a single sharp spot near the nuclear membrane, distinct from the spindle pole bodies and nucleolus. In dividing cells, the spot is exclusively present in the mother cell. The SHP box and the VCP-interaction motif (VIM) are important both together for binding to CDC48. The 2 SUMO interaction motifs (SIM) are each important for binding to SMT3(SUMO). Accumulates DPCs and exhibits gross chromosomal rearrangements. Belongs to the peptidase M3 family. WSS1-like metalloprotease (WLM) subfamily. Was initially reported to be a SUMO-dependent isopeptidase (PubMed:20516210), but this activity could not be confirmed (PubMed:24998930).