John Hemming's Web Log

I recently read a paper Ribonucleotide incorporation into mitochondrial DNA drives inflammation which I found very interesting. The reason I found it interesting is perhaps summarised in the first paragraph of the discussion section which I will quote: We demonstrate that increased incorporation of rNTPs into mtDNA during replication leads to the release of mtDNA fragments from mitochondria and proinflammatory signalling. Our results therefore highlight the challenge that the high molar excess of rNTPs relative to dNTPs poses to cells. Although RNase H2 removes incorporated rNMPs from nuclear DNA as part of the ribonucleotide excision repair pathway, this repair mechanism is not present in mitochondria, which are therefore prone to accumulating rNMPs in their genome. Similar to the effect of rNMPs on nuclear DNA replication27,40, due to the inherent reactivity of the 2′-OH group of the ribose ring or collisions with the replication fork, misincorporated rNMPs may cause DNA strand br...