Elimination of rNMPs from mitochondrial DNA has no effect on its stability
Journal article, 2020

Ribonucleotides (rNMPs) incorporated in the nuclear genome are a well-established threat to genome stability and can result in DNA strand breaks when not removed in a timely manner. However, the presence of a certain level of rNMPs is tolerated in mitochondrial DNA (mtDNA) although aberrant mtDNA rNMP content has been identified in disease models. We investigated the effect of incorporated rNMPs on mtDNA stability over the mouse life span and found that the mtDNA rNMP content increased during early life. The rNMP content of mtDNA varied greatly across different tissues and was defined by the rNTP/dNTP ratio of the tissue. Accordingly, mtDNA rNMPs were nearly absent in SAMHD1-/- mice that have increased dNTP pools. The near absence of rNMPs did not, however, appreciably affect mtDNA copy number or the levels of mtDNA molecules with deletions or strand breaks in aged animals near the end of their life span. The physiological rNMP load therefore does not contribute to the progressive loss of mtDNA quality that occurs as mice age.

dNTP pool

ribonucleotide incorporation

mitochondrial DNA




Paulina Wanrooij

Umeå University

Phong Tran

Umeå University

Liam J. Thompson

University of Gothenburg

Gustavo Carvalho

Umeå University

Sushma Sharma

Umeå University

Katrin Kreisel

University of Gothenburg

Clara Navarrete Roman

University of Gothenburg

Anna Lena Feldberg

Umeå University

Danielle L. Watt

Umeå University

Anna Karin Nilsson

Umeå University

Martin Engqvist

University of Gothenburg

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Anders R. Clausen

University of Gothenburg

Andrei Chabes

Umeå University

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 117 25 14306-14313

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Other Biological Topics

Medical Genetics






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