Toggle Main Menu Toggle Search

Open Access padlockePrints

Nucleotide pools dictate the identity and frequency of ribonucleotide incorporation in mitochondrial DNA

Lookup NU author(s): Professor Robert Taylor

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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

Year: 2017

Volume: 13

Issue: 2

Online publication date: 16/02/2017

Acceptance date: 09/02/2017

ISSN (print): 1553-7390

ISSN (electronic): 1553-7404

Publisher: Public Library of Science

URL: https://doi.org/10.1371/journal.pgen.1006628

DOI: 10.1371/journal.pgen.1006628


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share