Histone PARylation factor 1 (HPF1)

Histone PARylation factor 1 (HPF1) is a modulator of PARP1 and PARP2 activity critical for the cellular DNA damage response. HPF1 forms a joint active site with PARP1/PARP2, switching the ADP-ribosylation specificity from glutamate/aspartate to serine residues, primarily on histones, and thereby regulates chromatin modification and genome stability[1][3][4]. This factor not only directs PARP1-mediated poly(ADP-ribose) (PAR) chain formation onto histones but also controls chain length and suppresses excessive PARP1 automodification. Loss of HPF1 sensitizes cells to DNA damage and enhances the cytotoxicity of PARP inhibitors, defining HPF1 as a pivotal player in genome maintenance and a functional component at the intersection of DNA repair and therapeutic PARP inhibition[4]. HPF1 also interacts with drugs such as olaparib, impacting drug affinity to PARP complexes relevant for targeted cancer therapy[2].

Other names

C4orf27FLJ20534UPF0609 protein C4orf27

Modulation of PARP1/2 activity by facilitating serine PARylation of histones, influencing affinity and inhibition profile of PARP inhibitors[2][3]