For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases
DNA polymerases constitute a versatile group of enzymes that not only perform the essential task of genome duplication but also participate in various genome maintenance pathways, such as base and nucleotide excision repair, non-homologous end-joining, homologous recombination, and translesion synth...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/363 |
| _version_ | 1797358638368555008 |
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| author | Eva Balint Ildiko Unk |
| author_facet | Eva Balint Ildiko Unk |
| author_sort | Eva Balint |
| collection | DOAJ |
| description | DNA polymerases constitute a versatile group of enzymes that not only perform the essential task of genome duplication but also participate in various genome maintenance pathways, such as base and nucleotide excision repair, non-homologous end-joining, homologous recombination, and translesion synthesis. Polymerases catalyze DNA synthesis via the stepwise addition of deoxynucleoside monophosphates to the 3′ primer end in a partially double-stranded DNA. They require divalent metal cations coordinated by active site residues of the polymerase. Mg<sup>2+</sup> is considered the likely physiological activator because of its high cellular concentration and ability to activate DNA polymerases universally. Mn<sup>2+</sup> can also activate the known DNA polymerases, but in most cases, it causes a significant decrease in fidelity and/or processivity. Hence, Mn<sup>2+</sup> has been considered mutagenic and irrelevant during normal cellular function. Intriguingly, a growing body of evidence indicates that Mn<sup>2+</sup> can positively influence some DNA polymerases by conferring translesion synthesis activity or altering the substrate specificity. Here, we review the relevant literature focusing on the impact of Mn<sup>2+</sup> on the biochemical activity of a selected set of polymerases, namely, Polβ, Polλ, and Polµ, of the X family, as well as Polι and Polη of the Y family of polymerases, where congruous data implicate the physiological relevance of Mn<sup>2+</sup> in the cellular function of these enzymes. |
| first_indexed | 2024-03-08T15:04:56Z |
| format | Article |
| id | doaj.art-034b7afe9d8b4a3ca8683c83e40cda54 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:04:56Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-034b7afe9d8b4a3ca8683c83e40cda542024-01-10T14:59:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125136310.3390/ijms25010363For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA PolymerasesEva Balint0Ildiko Unk1Institute of Genetics, HUN-REN Biological Research Centre Szeged, H-6726 Szeged, HungaryInstitute of Genetics, HUN-REN Biological Research Centre Szeged, H-6726 Szeged, HungaryDNA polymerases constitute a versatile group of enzymes that not only perform the essential task of genome duplication but also participate in various genome maintenance pathways, such as base and nucleotide excision repair, non-homologous end-joining, homologous recombination, and translesion synthesis. Polymerases catalyze DNA synthesis via the stepwise addition of deoxynucleoside monophosphates to the 3′ primer end in a partially double-stranded DNA. They require divalent metal cations coordinated by active site residues of the polymerase. Mg<sup>2+</sup> is considered the likely physiological activator because of its high cellular concentration and ability to activate DNA polymerases universally. Mn<sup>2+</sup> can also activate the known DNA polymerases, but in most cases, it causes a significant decrease in fidelity and/or processivity. Hence, Mn<sup>2+</sup> has been considered mutagenic and irrelevant during normal cellular function. Intriguingly, a growing body of evidence indicates that Mn<sup>2+</sup> can positively influence some DNA polymerases by conferring translesion synthesis activity or altering the substrate specificity. Here, we review the relevant literature focusing on the impact of Mn<sup>2+</sup> on the biochemical activity of a selected set of polymerases, namely, Polβ, Polλ, and Polµ, of the X family, as well as Polι and Polη of the Y family of polymerases, where congruous data implicate the physiological relevance of Mn<sup>2+</sup> in the cellular function of these enzymes.https://www.mdpi.com/1422-0067/25/1/363DNA polymerasesmanganesetranslesion synthesiscatalytic activitypolymerase families |
| spellingShingle | Eva Balint Ildiko Unk For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases International Journal of Molecular Sciences DNA polymerases manganese translesion synthesis catalytic activity polymerase families |
| title | For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases |
| title_full | For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases |
| title_fullStr | For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases |
| title_full_unstemmed | For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases |
| title_short | For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases |
| title_sort | for the better or for the worse the effect of manganese on the activity of eukaryotic dna polymerases |
| topic | DNA polymerases manganese translesion synthesis catalytic activity polymerase families |
| url | https://www.mdpi.com/1422-0067/25/1/363 |
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