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

Tatyana A. Kurgina, Nina A. Moor, Mikhail M. Kutuzov, Konstantin N. Naumenko, Alexander A. Ukraintsev, Olga I. Lavrik

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование


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.

Язык оригиналаанглийский
Номер статьи1259
ЖурналCommunications Biology
Номер выпуска1
СостояниеОпубликовано - дек. 2021

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Подробные сведения о темах исследования «Dual function of HPF1 in the modulation of PARP1 and PARP2 activities». Вместе они формируют уникальный семантический отпечаток (fingerprint).