Single-stranded DNA-binding serine protease that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity. DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde. Protects replication fork from stalling by removing DPCs, such as covalently trapped topoisomerase 1 (TOP1) adducts on DNA lesion, or poly(ADP-ribose) polymerase 1 (PARP1)-DNA complexes trapped by PARP inhibitors. Required for PCNA loading on replication sites. Promotes S-phase entry and DNA synthesis. Interacts (via PIP-box) with PCNA; this interaction is direct. Mainly localizes to nucleus: colocalizes with PCNA on replication sites. The PIP-box mediates the interaction with PCNA. Autocatalytically cleaved; autocatalytic cleavage takes place in trans. Belongs to the FAM111 family.