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 (PubMed:32165630). 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 (PubMed:32165630). 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 (PubMed:32165630). Required for PCNA loading on replication sites (PubMed:24561620). Promotes S-phase entry and DNA synthesis (PubMed:24561620). (Microbial infection) May directly function at replication forks, explaining why Simian virus 40 (SV40) interacts with FAM111A to overcome host range restriction. Interacts (via PIP-box) with PCNA; then interaction is direct. (Microbial infection) Interacts with SV40 virus large T antigen and this interaction is required for efficient viral replication and sustained viral gene expression in restrictive cell types. Mainly localizes to nucleus: colocalizes with PCNA on replication sites. Regulated in a cell cycle dependent manner with the lowest expression during G0 or the quiescent phase and with peak expression during G2/M phase (at protein level). The PIP-box mediates the interaction with PCNA. Autocatalytically cleaved; activating the protein (PubMed:32165630). Autocatalytic cleavage takes place in trans (PubMed:32165630). The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Belongs to the FAM111 family. Truncated N-terminus. Extended N-terminus.