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Ribonucleotides incorporated by the yeast mitochondrial DNA polymerase are not repaired
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. (Andrei Chabes)
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. (Sjoerd Wanrooij)
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2017 (Engelska)Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, nr 47, s. 12466-12471, artikel-id 201713085Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
National Academy of Sciences , 2017. Vol. 114, nr 47, s. 12466-12471, artikel-id 201713085
Nyckelord [en]
DNA replication, dNTP, mitochondrial DNA, ribonucleotide excision repair, ribonucleotide incorporation
Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-141580DOI: 10.1073/pnas.1713085114ISI: 000416503700053PubMedID: 29109257OAI: oai:DiVA.org:umu-141580DiVA, id: diva2:1155535
Tillgänglig från: 2017-11-08 Skapad: 2017-11-08 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

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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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Institutionen för medicinsk kemi och biofysikMolekylär Infektionsmedicin, Sverige (MIMS)
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Proceedings of the National Academy of Sciences of the United States of America
Cell- och molekylärbiologi

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