Poly(ADP-ribose) polymerase 1 (PARP1) activity is regulated by its co-factor histone
poly(ADP-ribosylation) factor 1 (HPF1). The complex formed by HPF1 and PARP1 catalyzes
ADP-ribosylation of serine residues of proteins near DNA breaks, mainly PARP1 and
histones. However, the effect of HPF1 on DNA repair regulated by PARP1 remains unclear.
Here, we show that HPF1 controls prolonged histone ADP-ribosylation in the vicinity
of the DNA breaks by regulating both the number and length of ADP-ribose chains. Furthermore,
we demonstrate that HPF1-dependent histone ADP-ribosylation triggers the rapid unfolding
of chromatin, facilitating access to DNA at sites of damage. This process promotes
the assembly of both the homologous recombination and non-homologous end joining repair
machineries. Altogether, our data highlight the key roles played by the PARP1/HPF1
complex in regulating ADP-ribosylation signaling as well as the conformation of damaged
chromatin at early stages of the DNA damage response.Smith, Zentout et al. investigate
the role of HPF1 in DNA repair using live-cell imaging methods and find that HPF1-dependent
histone ADP-ribosylation drives early process in DNA repair, including chromatin relaxation
and repair factor recruitment.