Dual function of HPF1 in the modulation of PARP1 and PARP2 activities

  • Commun Biol. 2021 Nov 3;4(1):1259. doi: 10.1038/s42003-021-02780-0.
Tatyana A Kurgina  #  1  2 ,  Nina A Moor  #  1 ,  Mikhail M Kutuzov  1 ,  Konstantin N Naumenko  1 ,  Alexander A Ukraintsev  1 ,  Olga I Lavrik  3  4
Affiliations
  • 1. Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia.
  • 2. Novosibirsk State University, Novosibirsk, Russia.
  • 3. Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia. [email protected].
  • 4. Novosibirsk State University, Novosibirsk, Russia. [email protected].
  • # Contributed equally.
PMID: 34732825 DOI: 10.1038/s42003-021-02780-0
Abstract

Poly(ADP-ribosyl)ation catalyzed by poly(ADP-ribose) polymerases (PARPs) is one of the immediate cellular responses to DNA damage. The histone PARylation factor 1 (HPF1) discovered recently to form a joint active site with PARP1 and PARP2 was shown to limit the PARylation activity of PARPs and stimulate their NAD+-hydrolase activity. Here we demonstrate that HPF1 can stimulate the DNA-dependent and DNA-independent autoPARylation of PARP1 and PARP2 as well as the heteroPARylation of histones in the complex with nucleosome. The stimulatory action is detected in a defined range of HPF1 and NAD+ concentrations at which no HPF1-dependent enhancement in the hydrolytic NAD+ consumption occurs. PARP2, comparing with PARP1, is more efficiently stimulated by HPF1 in the autoPARylation reaction and is more active in the heteroPARylation of histones than in the automodification, suggesting a specific role of PARP2 in the ADP-ribosylation-dependent modulation of chromatin structure. Possible role of the dual function of HPF1 in the maintaining PARP activity is discussed.