TY - JOUR

T1 - The HPF1-dependent histone PARylation catalyzed by PARP2 is specifically stimulated by an incised AP site-containing BER DNA intermediate

AU - Kurgina, Tatyana A.

AU - Moor, Nina A.

AU - Kutuzov, Mikhail M.

AU - Lavrik, Olga I.

N1 - Funding Information: We would like to thank the entire laboratory of bioorganic chemistry of enzymes for feedback. We acknowledge Svetlana N. Khodyreva for guidance in preparation of NCP, Konstantin N. Naumenko, Alexander A. Uktaintsev and Ekaterina S. Ilina for preparation of recombinant proteins. The reported study was funded by RSFP № 121031300041-4 (use of shared equipment for experimental work) and by RSF № 22-14-00112 (PARPs activity testing in various conditions). Publisher Copyright: © 2022 Elsevier B.V.

PY - 2022/12

Y1 - 2022/12

N2 - Poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 are DNA-dependent poly(ADP-ribose)transferases localized in nucleus. They have a significant homology in the C-terminal catalytic domain structure but differ in their N-terminal DNA-binding parts. The structural difference has an impact on the interaction of PARP1 and PARP2 with DNA and their DNA-dependent activation. Here, we compare the interaction of PARP1 and PARP2 with free 147 bp nucleosomal DNA and its nucleosome-associated variant (NCP) that contain in one strand a 1-nucleotide gap with 5'-dRP (imitating the intermediate of Base Excision Repair) or no specific damage. The affinity of PARP2 for the DNA strongly depends on the gap presence and to a lesser extent on the association with nucleosomes, while PARP1 interacts primarily with blunt ends of all DNAs and with a lower affinity with the single-strand break. The activities of PARP1 and PARP2 in the autoPARylation reaction and heteromodification of histones are distinctly stimulated by HPF1, depending on the gap presence in activating DNA. The most significant HPF1-induced stimulation of the histone modification in the presence of gapped NCP is a peculiar feature of PARP2. We propose a specific regulatory role of PARP2 in the process of DNA repair in the context of chromatin.

AB - Poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 are DNA-dependent poly(ADP-ribose)transferases localized in nucleus. They have a significant homology in the C-terminal catalytic domain structure but differ in their N-terminal DNA-binding parts. The structural difference has an impact on the interaction of PARP1 and PARP2 with DNA and their DNA-dependent activation. Here, we compare the interaction of PARP1 and PARP2 with free 147 bp nucleosomal DNA and its nucleosome-associated variant (NCP) that contain in one strand a 1-nucleotide gap with 5'-dRP (imitating the intermediate of Base Excision Repair) or no specific damage. The affinity of PARP2 for the DNA strongly depends on the gap presence and to a lesser extent on the association with nucleosomes, while PARP1 interacts primarily with blunt ends of all DNAs and with a lower affinity with the single-strand break. The activities of PARP1 and PARP2 in the autoPARylation reaction and heteromodification of histones are distinctly stimulated by HPF1, depending on the gap presence in activating DNA. The most significant HPF1-induced stimulation of the histone modification in the presence of gapped NCP is a peculiar feature of PARP2. We propose a specific regulatory role of PARP2 in the process of DNA repair in the context of chromatin.

KW - DNA repair

KW - HPF1

KW - Nucleosome

KW - PARP1

KW - PARP2

KW - Poly(ADP-ribosyl)ation

KW - Poly ADP Ribosylation

KW - DNA/metabolism

KW - Poly(ADP-ribose) Polymerases/metabolism

KW - DNA Repair

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

KW - Nucleosomes

KW - Histones/genetics

KW - Catalysis

UR - http://www.scopus.com/inward/record.url?scp=85141270847&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/eadc6530-41e1-3f65-aabf-33f22b09b1bd/

U2 - 10.1016/j.dnarep.2022.103423

DO - 10.1016/j.dnarep.2022.103423

M3 - Article

C2 - 36356486

AN - SCOPUS:85141270847

VL - 120

JO - DNA Repair

JF - DNA Repair

SN - 1568-7864

M1 - 103423

ER -