PT  - JOURNAL ARTICLE
AU  - Paulina H. Wanrooij
AU  - Phong Tran
AU  - Liam J. Thompson
AU  - Sushma Sharma
AU  - Katrin Kreisel
AU  - Clara Navarrete
AU  - Anna-Lena Feldberg
AU  - Danielle L. Watt
AU  - Anna Karin Nilsson
AU  - Martin K. M. Engqvist
AU  - Anders R. Clausen
AU  - Andrei Chabes
TI  - The physiological level of rNMPs present in mtDNA does not compromise its stability
AID  - 10.1101/746719
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 746719
4099  - http://biorxiv.org/content/early/2020/04/09/746719.short
4100  - http://biorxiv.org/content/early/2020/04/09/746719.full
AB  - 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 lifespan 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 lifespan. The physiological rNMP load therefore does not contribute to the progressive loss of mtDNA quality that occurs as mice age.Competing Interest StatementThe authors have declared no competing interest.