Ribonucleotides incorporated by the yeast mitochondrial DNA polymerase are not repaired
Artikel i vetenskaplig tidskrift, 2017

Incorporation of ribonucleotides into DNA during genome replication is a significant source of genomic instability. The frequency of ribonucleotides in DNA is determined by deoxyribonucleoside triphosphate/ribonucleoside triphosphate (dNTP/rNTP) ratios, by the ability of DNA polymerases to discriminate against ribonucleotides, and by the capacity of repair mechanisms to remove incorporated ribonucleotides. To simultaneously compare how the nuclear and mitochondrial genomes incorporate and remove ribonucleotides, we challenged these processes by changing the balance of cellular dNTPs. Using a collection of yeast strains with altered dNTP pools, we discovered an inverse relationship between the concentration of individual dNTPs and the amount of the corresponding ribonucleotides incorporated in mitochondrial DNA, while in nuclear DNA the ribonucleotide pattern was only altered in the absence of ribonucleotide excision repair. Our analysis uncovers major differences in ribonucleotide repair between the two genomes and provides concrete evidence that yeast mitochondria lack mechanisms for removal of ribonucleotides incorporated by the mtDNA polymerase. Furthermore, as cytosolic dNTP pool imbalances were transmitted equally well into the nucleus and the mitochondria, our results support a view of the cytosolic and mitochondrial dNTP pools in frequent exchange.

DNTP

Mitochondrial DNA

Ribonucleotide excision repair

Ribonucleotide incorporation

DNA replication

Författare

Paulina Wanrooij

Umea universitet

Martin Engqvist

Chalmers, Biologi och bioteknik, Systembiologi

Josefin M.E. Forslund

Umea universitet

Clara Navarrete

Goteborgs universitet, Institutionen for biomedicin

Anna Karin Nilsson

Umea universitet

Juhan Sedman

University of Tartu

Sjoerd Wanrooij

Umea universitet

Anders R. Clausen

Goteborgs universitet, Institutionen for biomedicin

Andrei Chabes

Umea universitet

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 114 12466-12471

Ämneskategorier

Biologiska vetenskaper

DOI

10.1073/pnas.1713085114

PubMed

29109257