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Lookup NU author(s): Professor Robert Taylor
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© 2017 Berglund et al.Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA) and in the present study we use a genome-wide approach to precisely map the location of these. We find that ribonucleotides are distributed evenly between the heavy- and light-strand of mtDNA. The relative levels of incorporated ribonucleotides reflect that DNA polymerase γ discriminates the four ribonucleotides differentially during DNA synthesis. The observed pattern is also dependent on the mitochondrial deoxyribonucleotide (dNTP) pools and disease-causing mutations that change these pools alter both the absolute and relative levels of incorporated ribonucleotides. Our analyses strongly suggest that DNA polymerase γ-dependent incorporation is the main source of ribonucleotides in mtDNA and argues against the existence of a mitochondrial ribonucleotide excision repair pathway in human cells. Furthermore, we clearly demonstrate that when dNTP pools are limiting, ribonucleotides serve as a source of building blocks to maintain DNA replication. Increased levels of embedded ribonucleotides in patient cells with disturbed nucleotide pools may contribute to a pathogenic mechanism that affects mtDNA stability and impair new rounds of mtDNA replication.
Author(s): Berglund A-K, Navarrete C, Engqvist MKM, Hoberg E, Szilagyi Z, Taylor RW, Gustafsson CM, Falkenberg M, Clausen AR
Publication type: Article
Publication status: Published
Journal: PLoS Genetics
Online publication date: 16/02/2017
Acceptance date: 09/02/2017
Date deposited: 03/05/2017
ISSN (print): 1553-7390
ISSN (electronic): 1553-7404
Publisher: Public Library of Science
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