TY - JOUR

T1 - Dual function of HPF1 in the modulation of PARP1 and PARP2 activities

AU - Kurgina, Tatyana A.

AU - Moor, Nina A.

AU - Kutuzov, Mikhail M.

AU - Naumenko, Konstantin N.

AU - Ukraintsev, Alexander A.

AU - Lavrik, Olga I.

N1 - Funding Information: We would like to thank the entire laboratory of bioorganic chemistry of enzymes for feedback. We acknowledge Ekaterina A. Belousova for supporting initial stages of this work, and Svetlana N. Khodyreva for guidance in obtaining NCP. The reported study was funded by RFBR according to the research projects № 20-34-70028 (protein purification) and № 20-34-90095 (DNA and nucleosome construction), by RSFP № 121031300041-4 (use of shared equipment for experimental work), and by RSF № 21-64-00017 (PARPs activity testing in various conditions). Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

KW - Animals

KW - Carrier Proteins/genetics

KW - Histones/metabolism

KW - Humans

KW - Mice

KW - Nuclear Proteins/genetics

KW - Nucleosomes/metabolism

KW - Poly (ADP-Ribose) Polymerase-1/genetics

KW - Poly ADP Ribosylation

KW - Poly(ADP-ribose) Polymerases/genetics

UR - http://www.scopus.com/inward/record.url?scp=85118480020&partnerID=8YFLogxK

U2 - 10.1038/s42003-021-02780-0

DO - 10.1038/s42003-021-02780-0

M3 - Article

C2 - 34732825

AN - SCOPUS:85118480020

VL - 4

JO - Communications Biology

JF - Communications Biology

SN - 2399-3642

IS - 1

M1 - 1259

ER -