The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair
DNA polymerase β (Polβ) is considered the main repair DNA polymerase involved in the base excision repair (BER) pathway, which plays an important part in the repair of damaged DNA bases usually resulting from alkylation or oxidation. In general, BER involves consecutive actions of DNA glycosylases,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/2390 |
| _version_ | 1797479273774186496 |
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| author | Olga A. Kladova Olga S. Fedorova Nikita A. Kuznetsov |
| author_facet | Olga A. Kladova Olga S. Fedorova Nikita A. Kuznetsov |
| author_sort | Olga A. Kladova |
| collection | DOAJ |
| description | DNA polymerase β (Polβ) is considered the main repair DNA polymerase involved in the base excision repair (BER) pathway, which plays an important part in the repair of damaged DNA bases usually resulting from alkylation or oxidation. In general, BER involves consecutive actions of DNA glycosylases, AP endonucleases, DNA polymerases, and DNA ligases. It is known that protein–protein interactions of Polβ with enzymes from the BER pathway increase the efficiency of damaged base repair in DNA. However natural single-nucleotide polymorphisms can lead to a substitution of functionally significant amino acid residues and therefore affect the catalytic activity of the enzyme and the accuracy of Polβ action. Up-to-date databases contain information about more than 8000 SNPs in the gene of Polβ. This review summarizes data on the in silico prediction of the effects of Polβ SNPs on DNA repair efficacy; available data on cancers associated with SNPs of Polβ; and experimentally tested variants of Polβ. Analysis of the literature indicates that amino acid substitutions could be important for the maintenance of the native structure of Polβ and contacts with DNA; others affect the catalytic activity of the enzyme or play a part in the precise and correct attachment of the required nucleotide triphosphate. Moreover, the amino acid substitutions in Polβ can disturb interactions with enzymes involved in BER, while the enzymatic activity of the polymorphic variant may not differ significantly from that of the wild-type enzyme. Therefore, investigation regarding the effect of Polβ natural variants occurring in the human population on enzymatic activity and protein–protein interactions is an urgent scientific task. |
| first_indexed | 2024-03-09T21:43:30Z |
| format | Article |
| id | doaj.art-d36857ae13e34cdc9854329d7cc4ccc8 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:43:30Z |
| publishDate | 2022-02-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d36857ae13e34cdc9854329d7cc4ccc82023-11-23T20:24:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234239010.3390/ijms23042390The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA RepairOlga A. Kladova0Olga S. Fedorova1Nikita A. Kuznetsov2Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaDNA polymerase β (Polβ) is considered the main repair DNA polymerase involved in the base excision repair (BER) pathway, which plays an important part in the repair of damaged DNA bases usually resulting from alkylation or oxidation. In general, BER involves consecutive actions of DNA glycosylases, AP endonucleases, DNA polymerases, and DNA ligases. It is known that protein–protein interactions of Polβ with enzymes from the BER pathway increase the efficiency of damaged base repair in DNA. However natural single-nucleotide polymorphisms can lead to a substitution of functionally significant amino acid residues and therefore affect the catalytic activity of the enzyme and the accuracy of Polβ action. Up-to-date databases contain information about more than 8000 SNPs in the gene of Polβ. This review summarizes data on the in silico prediction of the effects of Polβ SNPs on DNA repair efficacy; available data on cancers associated with SNPs of Polβ; and experimentally tested variants of Polβ. Analysis of the literature indicates that amino acid substitutions could be important for the maintenance of the native structure of Polβ and contacts with DNA; others affect the catalytic activity of the enzyme or play a part in the precise and correct attachment of the required nucleotide triphosphate. Moreover, the amino acid substitutions in Polβ can disturb interactions with enzymes involved in BER, while the enzymatic activity of the polymorphic variant may not differ significantly from that of the wild-type enzyme. Therefore, investigation regarding the effect of Polβ natural variants occurring in the human population on enzymatic activity and protein–protein interactions is an urgent scientific task.https://www.mdpi.com/1422-0067/23/4/2390DNA repairDNA polymerase betasingle-nucleotide polymorphismprotein–protein interactionenzymatic activityDNA repair coordination |
| spellingShingle | Olga A. Kladova Olga S. Fedorova Nikita A. Kuznetsov The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair International Journal of Molecular Sciences DNA repair DNA polymerase beta single-nucleotide polymorphism protein–protein interaction enzymatic activity DNA repair coordination |
| title | The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair |
| title_full | The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair |
| title_fullStr | The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair |
| title_full_unstemmed | The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair |
| title_short | The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair |
| title_sort | role of natural polymorphic variants of dna polymerase β in dna repair |
| topic | DNA repair DNA polymerase beta single-nucleotide polymorphism protein–protein interaction enzymatic activity DNA repair coordination |
| url | https://www.mdpi.com/1422-0067/23/4/2390 |
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