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
SAMHD1
mtDNA
Author
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 14306-14313Subject Categories
Other Biological Topics
Medical Genetics
Genetics
DOI
10.1073/pnas.1916851117
PubMed
32513727