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Ribonucleotides incorporated by the yeast mitochondrial DNA polymerase are not repaired
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. (Andrei Chabes)
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. (Sjoerd Wanrooij)
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2017 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 47, p. 12466-12471, article id 201713085Article in journal (Refereed) Published
Abstract [en]

Incorporation of ribonucleotides into DNA during genome replication is a significant source of genomic instability. The frequency of ribonucleotides in DNA is determined by deoxyribonucleoside triphosphate/ribonucleoside triphosphate (dNTP/rNTP) ratios, by the ability of DNA polymerases to discriminate against ribonucleotides, and by the capacity of repair mechanisms to remove incorporated ribonucleotides. To simultaneously compare how the nuclear and mitochondrial genomes incorporate and remove ribonucleotides, we challenged these processes by changing the balance of cellular dNTPs. Using a collection of yeast strains with altered dNTP pools, we discovered an inverse relationship between the concentration of individual dNTPs and the amount of the corresponding ribonucleotides incorporated in mitochondrial DNA, while in nuclear DNA the ribonucleotide pattern was only altered in the absence of ribonucleotide excision repair. Our analysis uncovers major differences in ribonucleotide repair between the two genomes and provides concrete evidence that yeast mitochondria lack mechanisms for removal of ribonucleotides incorporated by the mtDNA polymerase. Furthermore, as cytosolic dNTP pool imbalances were transmitted equally well into the nucleus and the mitochondria, our results support a view of the cytosolic and mitochondrial dNTP pools in frequent exchange.

Place, publisher, year, edition, pages
National Academy of Sciences , 2017. Vol. 114, no 47, p. 12466-12471, article id 201713085
Keywords [en]
DNA replication, dNTP, mitochondrial DNA, ribonucleotide excision repair, ribonucleotide incorporation
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-141580DOI: 10.1073/pnas.1713085114ISI: 000416503700053PubMedID: 29109257OAI: oai:DiVA.org:umu-141580DiVA, id: diva2:1155535
Available from: 2017-11-08 Created: 2017-11-08 Last updated: 2018-06-09Bibliographically approved

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Wanrooij, Paulina H.Forslund, Josefin M. E.Nilsson, Anna KarinWanrooij, SjoerdChabes, Andrei

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Wanrooij, Paulina H.Forslund, Josefin M. E.Nilsson, Anna KarinWanrooij, SjoerdChabes, Andrei
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Department of Medical Biochemistry and BiophysicsMolecular Infection Medicine Sweden (MIMS)
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Proceedings of the National Academy of Sciences of the United States of America
Cell and Molecular Biology

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