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

Bakman, Artemiy S.; Boichenko, Stanislav S.; Kuznetsova, Aleksandra A.; Ishchenko, Alexander A.; Saparbaev, Murat; Kuznetsov, Nikita A.

doi:10.1016/j.biochi.2023.10.007

Cited by 2 publications

(1 citation statement)

References 57 publications

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“…Moreover, stopped-flow analysis of Polβ interaction with DNA and dNTPs has been well characterized by means of 2-aPu fluorescence intensity changes [41,42,57,58]. It has been stated that two-stage changes in fluorescence intensity of a 2-aPu residue correspond to (i) the stage of formation of a ternary closed complex of the enzyme, DNA, and dNTP (an increase phase) and to (ii) the chemical stage of transfer of the dNMP residue to the 3 ′ end of a primer and formation of the reaction product (a phase of a decrease in fluorescence intensity) [57][58][59][60].…”

Section: Effects Of the Amino Acid Residue Substitutions On The Bindi...mentioning

confidence: 99%

The Impact of SNP-Induced Amino Acid Substitutions L19P and G66R in the dRP-Lyase Domain of Human DNA Polymerase β on Enzyme Activities

Kladova,

Tyugashev,

Yakimov

et al. 2024

IJMS

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Base excision repair (BER), which involves the sequential activity of DNA glycosylases, apurinic/apyrimidinic endonucleases, DNA polymerases, and DNA ligases, is one of the enzymatic systems that preserve the integrity of the genome. Normal BER is effective, but due to single-nucleotide polymorphisms (SNPs), the enzymes themselves—whose main function is to identify and eliminate damaged bases—can undergo amino acid changes. One of the enzymes in BER is DNA polymerase β (Polβ), whose function is to fill gaps in DNA. SNPs can significantly affect the catalytic activity of an enzyme by causing an amino acid substitution. In this work, pre-steady-state kinetic analyses and molecular dynamics simulations were used to examine the activity of naturally occurring variants of Polβ that have the substitutions L19P and G66R in the dRP-lyase domain. Despite the substantial distance between the dRP-lyase domain and the nucleotidyltransferase active site, it was found that the capacity to form a complex with DNA and with an incoming dNTP is significantly altered by these substitutions. Therefore, the lower activity of the tested polymorphic variants may be associated with a greater number of unrepaired DNA lesions.

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Section: Effects Of the Amino Acid Residue Substitutions On The Bindi...mentioning

confidence: 99%

The Impact of SNP-Induced Amino Acid Substitutions L19P and G66R in the dRP-Lyase Domain of Human DNA Polymerase β on Enzyme Activities

Kladova,

Tyugashev,

Yakimov

et al. 2024

IJMS

Self Cite

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Role of the Nrf2/ARE Pathway in the mtDNA Reparation

Gureev,

Chernyshova,

Krutskikh

et al. 2024

Front. Biosci. (Landmark Ed)

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Mitochondrial DNA (mtDNA) is located in the mitochondrial matrix, in close proximity to major sources of reactive oxygen species (ROS) in the cell. This makes mtDNA one of the most susceptible components to damage in the cell. The nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway is an important cytoprotective mechanism. It is well-studied and described that Nrf2 can regulate the expression of mitochondrial-targeted antioxidant systems in the cell, indirectly protecting mtDNA from damage. However, the Nrf2/ARE pathway can also directly impact on the mtDNA repair processes. In this review, we summarize the existing data on the impact of Nrf2 on mtDNA repair, primarily base excision repair (BER), as it is considered the main repair pathway for the mitochondrial genome. We explore the crosstalk between Nrf2/ARE, BRCA1, and p53 signaling pathways in their involvement in maintaining mtDNA integrity. The role of other repair mechanisms in correcting mismatched bases and double-strand breaks is discussed. Additionally, the review addresses the role of Nrf2 in the repair of noncanonical bases, which contribute to an increased number of mutations in mtDNA and can contaminate the nucleotide pool.

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

Cited by 2 publications

References 57 publications

The Impact of SNP-Induced Amino Acid Substitutions L19P and G66R in the dRP-Lyase Domain of Human DNA Polymerase β on Enzyme Activities

The Impact of SNP-Induced Amino Acid Substitutions L19P and G66R in the dRP-Lyase Domain of Human DNA Polymerase β on Enzyme Activities

Role of the Nrf2/ARE Pathway in the mtDNA Reparation

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