Cofactor for serine ADP-ribosylation that confers serine specificity on PARP1 and PARP2 and plays a key role in DNA damage response (PubMed:28190768, PubMed:29480802, PubMed:29954836, PubMed:32028527, PubMed:32939087, PubMed:33186521, PubMed:33589610, PubMed:33683197, PubMed:34108479, PubMed:34210965, PubMed:34486521, PubMed:34625544, PubMed:34732825, PubMed:34795260, PubMed:34874266). 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). {ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29480802, ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197, ECO:0000269|PubMed:34108479, ECO:0000269|PubMed:34210965, ECO:0000269|PubMed:34486521, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266}. This is the function of ENSG00000056050 (HPF1, histone PARylation factor 1).