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.

mtDNA

ribonucleotide incorporation

dNTP pool

SAMHD1

mitochondrial DNA

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 14306-14313

Ämneskategorier

Annan biologi

Medicinsk genetik

Genetik

DOI

10.1073/pnas.1916851117

PubMed

32513727

Mer information

Senast uppdaterat

2020-09-01