{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:40:38Z","timestamp":1790779238254,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T00:00:00Z","timestamp":1640476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development and Innovation Office Hungary","award":["GINOP-2.3.2-15-2016-00024"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>DNA polymerase \u03b7 (Pol\u03b7) is a translesion synthesis polymerase that can bypass different DNA lesions with varying efficiency and fidelity. Its most well-known function is the error-free bypass of ultraviolet light-induced cyclobutane pyrimidine dimers. The lack of this unique ability in humans leads to the development of a cancer-predisposing disease, the variant form of xeroderma pigmentosum. Human Pol\u03b7 can insert rNTPs during DNA synthesis, though with much lower efficiency than dNTPs, and it can even extend an RNA chain with ribonucleotides. We have previously shown that Mn2+ is a specific activator of the RNA synthetic activity of yeast Pol\u03b7 that increases the efficiency of the reaction by several thousand-fold over Mg2+. In this study, our goal was to investigate the metal cofactor dependence of RNA synthesis by human Pol\u03b7. We found that out of the investigated metal cations, only Mn2+ supported robust RNA synthesis. Steady state kinetic analysis showed that Mn2+ activated the reaction a thousand-fold compared to Mg2+, even during DNA damage bypass opposite 8-oxoG and TT dimer. Our results revealed a two order of magnitude higher affinity of human Pol\u03b7 towards ribonucleotides in the presence of Mn2+ compared to Mg2+. It is noteworthy that activation occurred without lowering the base selectivity of the enzyme on undamaged templates, whereas the fidelity decreased across a TT dimer. In summary, our data strongly suggest that, like with its yeast homolog, Mn2+ is the proper metal cofactor of hPol\u03b7 during RNA chain extension, and selective metal cofactor utilization contributes to switching between its DNA and RNA synthetic activities.<\/jats:p>","DOI":"10.3390\/ijms23010230","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:00:54Z","timestamp":1640566854000},"page":"230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Manganese Is a Strong Specific Activator of the RNA Synthetic Activity of Human Pol\u03b7"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1258-6892","authenticated-orcid":false,"given":"Eva","family":"Balint","sequence":"first","affiliation":[{"name":"Biological Research Centre, Institute of Genetics, Eotvos Lor\u00e1nd Research Network, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8638-0339","authenticated-orcid":false,"given":"Ildiko","family":"Unk","sequence":"additional","affiliation":[{"name":"Biological Research Centre, Institute of Genetics, Eotvos Lor\u00e1nd Research Network, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev.biochem.74.082803.133250","article-title":"EUKARYOTIC TRANSLESION SYNTHESIS DNA POLYMERASES: Specificity of Structure and Function","volume":"74","author":"Prakash","year":"2005","journal-title":"Annu. 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