Molecular Cell
Volume 62, Issue 3, 5 May 2016, Pages 432-442
Journal home page for Molecular Cell

Short Article
HPF1/C4orf27 Is a PARP-1-Interacting Protein that Regulates PARP-1 ADP-Ribosylation Activity

https://doi.org/10.1016/j.molcel.2016.03.008Get rights and content
Under a Creative Commons license
open access

Highlights

  • Histone PARylation factor 1 (HPF1) is a component of the DNA damage response

  • HPF1 interacts with PARP-1 in cells via the PARP-1 catalytic domain

  • Loss of HPF1 sensitizes human cells to DNA damaging agents and PARP inhibition

  • HPF1 promotes PARP-1-dependent ADP-ribosylation of histones

Summary

We report the identification of histone PARylation factor 1 (HPF1; also known as C4orf27) as a regulator of ADP-ribosylation signaling in the DNA damage response. HPF1/C4orf27 forms a robust protein complex with PARP-1 in cells and is recruited to DNA lesions in a PARP-1-dependent manner, but independently of PARP-1 catalytic ADP-ribosylation activity. Functionally, HPF1 promotes PARP-1-dependent in trans ADP-ribosylation of histones and limits DNA damage-induced hyper-automodification of PARP-1. Human cells lacking HPF1 exhibit sensitivity to DNA damaging agents and PARP inhibition, thereby suggesting an important role for HPF1 in genome maintenance and regulating the efficacy of PARP inhibitors. Collectively, our results demonstrate how a fundamental step in PARP-1-dependent ADP-ribosylation signaling is regulated and suggest that HPF1 functions at the crossroads of histone ADP-ribosylation and PARP-1 automodification.

Cited by (0)