Elimination of rNMPs from mitochondrial DNA has no effect on its stability
Artikel i vetenskaplig tidskrift, 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
Författare
Paulina Wanrooij
Umeå universitet
Phong Tran
Umeå universitet
Liam J. Thompson
Göteborgs universitet
Gustavo Carvalho
Umeå universitet
Sushma Sharma
Umeå universitet
Katrin Kreisel
Göteborgs universitet
Clara Navarrete Roman
Göteborgs universitet
Anna Lena Feldberg
Umeå universitet
Danielle L. Watt
Umeå universitet
Anna Karin Nilsson
Umeå universitet
Martin Engqvist
Göteborgs universitet
Chalmers, Biologi och bioteknik, Systembiologi
Anders R. Clausen
Göteborgs universitet
Andrei Chabes
Umeå universitet
Proceedings of the National Academy of Sciences of the United States of America
0027-8424 (ISSN) 1091-6490 (eISSN)
Vol. 117 25 14306-14313Ämneskategorier
Annan biologi
Medicinsk genetik
Genetik
DOI
10.1073/pnas.1916851117
PubMed
32513727