Elimination of rNMPs from mitochondrial DNA has no effect on its stability

Proceedings of the National Academy of Sciences of the United States of America
Paulina H WanrooijAndrei Chabes

Abstract

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.

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Citations

May 22, 2021·Antioxidants & Redox Signaling·Gustavo CarvalhoPaulina H Wanrooij

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Datasets Mentioned

BETA
GSE133584

Methods Mentioned

BETA
electrophoresis
HydEn-Seq
PCR
DNA shearing

Software Mentioned

GraphPad Prism
LightCycler 96
ImageJ64
HydEn
Bowtie

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