Ribonucleotides Incorporated by the Yeast Mitochondrial DNA Polymerase Are Not Repaired

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2017 Nov 8

PMID 29109257

Citations 24

Authors

Paulina H Wanrooij

Martin K M Engqvist

Josefin M E Forslund

Clara Navarrete

Anna Karin Nilsson

Juhan Sedman

Sjoerd Wanrooij

Anders R Clausen

Andrei Chabes

Affiliations

Soon will be listed here.

Abstract

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.

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