Cofactor for serine ADP-ribosylation that confers serine specificity on PARP1 and PARP2 and plays a key role in DNA damage response. 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. 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. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. 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. HPF1 also promotes tyrosine ADP-ribosylation, probably by conferring tyrosine specificity on PARP1. Interacts with PARP1 (via the PARP catalytic domain). Interacts with PARP2 (via the PARP catalytic domain). Interacts with core nucleosomes in a PARP1- and PARP2-dependent manner. Localizes to DNA damage sites; chromatin localization is dependent on PARP1 and PARP2. Belongs to the HPF1 family.