TY - JOUR

T1 - Coordination between human DNA polymerase β and apurinic/apyrimidinic endonuclease 1 in the course of DNA repair

AU - Bakman, Artemiy S

AU - Boichenko, Stanislav S

AU - Kuznetsova, Aleksandra A

AU - Ishchenko, Alexander A

AU - Saparbaev, Murat

AU - Kuznetsov, Nikita A

N1 - This work was supported by the Ministry of Science and Higher Education of the Russian Federation, agreement No. 075-15-2022-263. M.S. was supported by a grant from the French National Research Agency (ANR–AAPG2022 MITOMUTREP), grants from the Electricité de France (RB2020–02 and RB 2021–05), and a grant (No. AP08856811) from the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan. A.A.I. was supported by a grant from Fondation ARC (PJA–2021060003796). Copyright © 2023. Published by Elsevier B.V.

PY - 2024/1

Y1 - 2024/1

N2 - Coordination of enzymatic activities in the course of base excision repair (BER) is essential to ensure complete repair of damaged bases. Two major mechanisms underlying the coordination of BER are known today: the "passing the baton" model and a model of preassembled stable multiprotein repair complexes called "repairosomes." In this work, we aimed to elucidate the coordination between human apurinic/apyrimidinic (AP) endonuclease APE1 and DNA polymerase Polβ in BER through studying an impact of APE1 on Polβ-catalyzed nucleotide incorporation into different model substrates that mimic different single-strand break (SSB) intermediates arising along the BER pathway. It was found that APE1's impact on separate stages of Polβ's catalysis depends on the nature of a DNA substrate. In this complex, APE1 removed 3' blocking groups and corrected Polβ-catalyzed DNA synthesis in a coordinated manner. Our findings support the hypothesis that Polβ not only can displace APE1 from damaged DNA within the "passing the baton" model but also performs the gap-filling reaction in the ternary complex with APE1 according to the "repairosome" model. Taken together, our results provide new insights into coordination between APE1 and Polβ during the BER process.

AB - Coordination of enzymatic activities in the course of base excision repair (BER) is essential to ensure complete repair of damaged bases. Two major mechanisms underlying the coordination of BER are known today: the "passing the baton" model and a model of preassembled stable multiprotein repair complexes called "repairosomes." In this work, we aimed to elucidate the coordination between human apurinic/apyrimidinic (AP) endonuclease APE1 and DNA polymerase Polβ in BER through studying an impact of APE1 on Polβ-catalyzed nucleotide incorporation into different model substrates that mimic different single-strand break (SSB) intermediates arising along the BER pathway. It was found that APE1's impact on separate stages of Polβ's catalysis depends on the nature of a DNA substrate. In this complex, APE1 removed 3' blocking groups and corrected Polβ-catalyzed DNA synthesis in a coordinated manner. Our findings support the hypothesis that Polβ not only can displace APE1 from damaged DNA within the "passing the baton" model but also performs the gap-filling reaction in the ternary complex with APE1 according to the "repairosome" model. Taken together, our results provide new insights into coordination between APE1 and Polβ during the BER process.

KW - Apurinic/apyrimidinic endonuclease

KW - Conformational change

KW - DNA repair

KW - DNA-protein interaction

KW - Damaged-DNA transfer

KW - Fluorescence

KW - Pre-steady-state kinetics

KW - Protein-protein interaction

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85173816495&origin=inward&txGid=7485945d7afe62758bdb4cf0063aa4e2

UR - https://www.mendeley.com/catalogue/bf4e8879-6205-342e-a6d0-9bca0051bcc4/

U2 - 10.1016/j.biochi.2023.10.007

DO - 10.1016/j.biochi.2023.10.007

M3 - Article

C2 - 37806619

VL - 216

SP - 126

EP - 136

JO - Biochimie

JF - Biochimie

SN - 0300-9084

ER -