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Initiates the repair of double-strand DNA breaks: recruited to DNA damage sites by PARP1 and PARP2 and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues, licensing serine ADP-ribosylation of target proteins (PubMed:28190768, PubMed:29480802, PubMed:29954836, PubMed:32028527, PubMed:32939087, PubMed:33589610, PubMed:33683197, PubMed:34486521, PubMed:34625544, PubMed:34732825, PubMed:34795260, PubMed:34874266). Serine ADP-ribosylation of target proteins, such as histones, promotes decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:27067600, PubMed:28190768, PubMed:32939087, PubMed:33589610). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802). HPF1 acts by completing the active site of PARP1 and PARP2: forms a composite active site composed of residues from HPF1 and PARP1 or PARP2 (PubMed:32028527, PubMed:33589610). While HPF1 promotes the initiation of serine ADP-ribosylation, it restricts the polymerase activity of PARP1 and PARP2 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). HPF1 also promotes tyrosine ADP-ribosylation, probably by conferring tyrosine specificity on PARP1 (PubMed:29954836, PubMed:30257210)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27067600"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32028527"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32939087"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33141820"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33589610"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34108479"}],"value":"Interacts with PARP1 (via the PARP catalytic domain) (PubMed:27067600, PubMed:32028527, PubMed:33589610). Interacts with PARP2 (via the PARP catalytic domain) (PubMed:27067600, PubMed:32028527, PubMed:32939087, PubMed:33141820, PubMed:34108479). Interacts with core nucleosomes in a PARP1- and PARP2-dependent manner (PubMed:27067600, PubMed:32939087)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9NWY4","intActId":"EBI-720597"},"interactantTwo":{"uniProtKBAccession":"Q9UL63","geneName":"MKLN1","intActId":"EBI-1048053"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27067600"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32939087"}],"value":"Localizes to DNA damage sites; chromatin localization is dependent on PARP1 and PARP2"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27067600"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32939087"}],"value":"Chromosome","id":"SL-0468"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27067600"}],"value":"Nucleus","id":"SL-0191"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the HPF1 family"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Protein Spotlight","resourceUrl":"https://www.proteinspotlight.org/back_issues/235/","ftp":false,"note":"Catalysis - 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