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:33186521, PubMed:32028527, PubMed:32939087). 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). 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). 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). HPF1 also promotes tyrosine ADP-ribosylation, probably by conferring tyrosine specificity on PARP1 (PubMed:30257210, PubMed:29954836). Interacts with PARP1 (via the PARP catalytic domain) (PubMed:27067600, PubMed:32028527). Interacts with PARP2 (via the PARP catalytic domain) (PubMed:27067600, PubMed:33141820, PubMed:32028527, PubMed:32939087). Interacts with core nucleosomes in a PARP1- and PARP2-dependent manner (PubMed:27067600, PubMed:32939087). Localizes to DNA damage sites; chromatin localization is dependent on PARP1 and PARP2. Belongs to the HPF1 family. Catalysis - Issue 235 of April 2021