E3 ubiquitin ligase required to protect genome stability in response to replication stress (PubMed:30979826, PubMed:30849395, PubMed:30842657). Acts as a key regulator of interstrand cross-link repair, which takes place when both strands of duplex DNA are covalently tethered together, thereby blocking replication and transcription (PubMed:30979826, PubMed:30849395, PubMed:30842657). Controls the choice between the two pathways of replication-coupled interstrand-cross-link repair by mediating ubiquitination of mcm7 subunit of the CMG helicase complex (PubMed:30842657). Short ubiquitin chains on mcm7 promote recruitment of DNA glycosylase neil3 (PubMed:30842657). If the interstrand cross-link cannot be cleaved by neil3, the ubiquitin chains continue to grow on mcm7, promoting the unloading of the CMG helicase complex by the vcp/p97 ATPase, enabling the Fanconi anemia DNA repair pathway (PubMed:30979826, PubMed:30842657). Only catalyzes ubiquitination of mcm7 when forks converge (PubMed:30842657). Also involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis: promotes ubiquitination of DPCs, leading to their degradation by the proteasome (PubMed:30595436). Also acts as a negative regulator of innate immune signaling by inhibiting activation of NF-kappa-B mediated by TNF (By similarity). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Localizes to DNA damage sites in response to replication stress. Belongs to the TRAIP family.