For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases

Bálint, Éva and Unk, Ildikó (2024) For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25 (1). No.-363. ISSN 1661-6596

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Abstract

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. Mg2+ is considered the likely physiological activator because of its high cellular concentration and ability to activate DNA polymerases universally. Mn2+ can also activate the known DNA polymerases, but in most cases, it causes a significant decrease in fidelity and/or processivity. Hence, Mn2+ has been considered mutagenic and irrelevant during normal cellular function. Intriguingly, a growing body of evidence indicates that Mn2+ 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 Mn2+ on the biochemical activity of a selected set of polymerases, namely, Pol beta, Pol lambda, and Pol mu, of the X family, as well as Pol iota and Pol eta of the Y family of polymerases, where congruous data implicate the physiological relevance of Mn2+ in the cellular function of these enzymes.

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