TY - JOUR

T1 - Apurinic/Apyrimidinic Endonuclease 1 and Tyrosyl-DNA Phosphodiesterase 1 Prevent Suicidal Covalent DNA-Protein Crosslink at Apurinic/Apyrimidinic Site

AU - Lebedeva, Natalia A.

AU - Rechkunova, Nadejda I.

AU - Endutkin, Anton V.

AU - Lavrik, Olga I.

N1 - Funding Information: The work was supported by the Russian Science Foundation (grant no. 20-14-00086) and Russian State Funded Budget Project (grant number AAAA-A17-117020210022-4, for OL). The proteins’ PARylation analysis was supported by the Russian Foundation for Basic Research (grant no. 19-04-00481). Publisher Copyright: © Copyright © 2021 Lebedeva, Rechkunova, Endutkin and Lavrik. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/1/11

Y1 - 2021/1/11

N2 - Bifunctional 8-oxoguanine-DNA glycosylase (OGG1), a crucial DNA-repair enzyme, removes from DNA 8-oxo-7,8-dihydroguanine (8-oxoG) with following cleavage of the arising apurinic/apyrimidinic (AP) site. The major enzyme in eukaryotic cells that catalyzes the cleavage of AP sites is AP endonuclease 1 (APE1). Alternatively, AP sites can be cleaved by tyrosyl-DNA phosphodiesterase 1 (TDP1) to initiate APE1-independent repair, thus expanding the ability of the base excision repair (BER) process. Poly(ADP-ribose) polymerase 1 (PARP1) is a regulatory protein of DNA repair. PARP2 is also activated in response to DNA damage and can be regarded as the BER participant. Here we analyze PARP1 and PARP2 interactions with DNA intermediates of the initial stages of the BER process (8-oxoG and AP-site containing DNA) and their interplay with the proteins recognizing and processing these DNA structures focusing on OGG1. OGG1 as well as PARP1 and PARP2 form covalent complex with AP site-containing DNA without borohydride reduction. AP site incision by APE1 or TDP1 removal of protein adducts but not proteins’ PARylation prevent DNA-protein crosslinks.

AB - Bifunctional 8-oxoguanine-DNA glycosylase (OGG1), a crucial DNA-repair enzyme, removes from DNA 8-oxo-7,8-dihydroguanine (8-oxoG) with following cleavage of the arising apurinic/apyrimidinic (AP) site. The major enzyme in eukaryotic cells that catalyzes the cleavage of AP sites is AP endonuclease 1 (APE1). Alternatively, AP sites can be cleaved by tyrosyl-DNA phosphodiesterase 1 (TDP1) to initiate APE1-independent repair, thus expanding the ability of the base excision repair (BER) process. Poly(ADP-ribose) polymerase 1 (PARP1) is a regulatory protein of DNA repair. PARP2 is also activated in response to DNA damage and can be regarded as the BER participant. Here we analyze PARP1 and PARP2 interactions with DNA intermediates of the initial stages of the BER process (8-oxoG and AP-site containing DNA) and their interplay with the proteins recognizing and processing these DNA structures focusing on OGG1. OGG1 as well as PARP1 and PARP2 form covalent complex with AP site-containing DNA without borohydride reduction. AP site incision by APE1 or TDP1 removal of protein adducts but not proteins’ PARylation prevent DNA-protein crosslinks.

KW - 8-oxoguanine-DNA glycosylase

KW - AP endonuclease 1

KW - apurinic/apyrimidinic site

KW - DNA-protein crosslinks

KW - poly(ADP-ribose) polymerases

KW - tyrosyl-DNA phosphodiesterase 1

UR - http://www.scopus.com/inward/record.url?scp=85099753944&partnerID=8YFLogxK

U2 - 10.3389/fcell.2020.617301

DO - 10.3389/fcell.2020.617301

M3 - Article

C2 - 33505969

AN - SCOPUS:85099753944

VL - 8

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

SN - 2296-634X

M1 - 617301

ER -