2022
DOI: 10.1093/nar/gkab1251
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Ribonucleotides embedded in template DNA impair mitochondrial RNA polymerase progression

Abstract: Human mitochondria lack ribonucleotide excision repair pathways, causing misincorporated ribonucleotides (rNMPs) to remain embedded in the mitochondrial genome. Previous studies have demonstrated that human mitochondrial DNA polymerase γ can bypass a single rNMP, but that longer stretches of rNMPs present an obstacle to mitochondrial DNA replication. Whether embedded rNMPs also affect mitochondrial transcription has not been addressed. Here we demonstrate that mitochondrial RNA polymerase elongation activity i… Show more

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Cited by 5 publications
(3 citation statements)
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“…The human mitochondrial genome is composed of a 16.6 kb circular double-stranded DNA molecule (mitochondrial DNA, mtDNA) that encodes key catalytic subunits essential for OXPHOS 12 . Of note, the mtDNA copy number is increased in most CC cells 13 .…”
Section: Introductionmentioning
confidence: 99%
“…The human mitochondrial genome is composed of a 16.6 kb circular double-stranded DNA molecule (mitochondrial DNA, mtDNA) that encodes key catalytic subunits essential for OXPHOS 12 . Of note, the mtDNA copy number is increased in most CC cells 13 .…”
Section: Introductionmentioning
confidence: 99%
“…1b), DNA embedded rNs can lead to nicks on the phosphate backbone and the accumulation of nonsynonymous mutations (11,15). These rNs, if left incorporated on the nuclear or mitochondria template strand, can lead to error-prone impairment and stalling of the replication and transcription machinery (16)(17)(18)(19). Because of their lethal nature, the cell has evolved two specific pathways to remove DNA-embedded rNs.…”
Section: Introductionmentioning
confidence: 99%
“…2 A ), DNA embedded rNs can lead to nicks on the phosphate backbone and the accumulation of nonsynonymous mutations ( 20 , 24 ). Although rN incorporation does not significantly affect the processivity of Pol η, Pol α, Pol δ, and Pol ε ( 25 , 26 ), rNs, if left incorporated on the nuclear or mitochondria template strand, can lead to error-prone impairment and stalling of the replication and transcription machinery ( 26 , 27 , 28 , 29 ). Because of their lethal nature, the cell has evolved two specific pathways to remove DNA-embedded rNs.…”
mentioning
confidence: 99%