Thursday, 3 May 2018

Linear mitochondrial DNA is rapidly degraded by components of the replication machinery

https://www.nature.com/articles/s41467-018-04131-w

Peeva V, Blei D, Trombly G, Corsi S, Szukszto MJ, Rebelo-Guiomar P, Gammage PA, Kudin AP, Becker C, Altmüller J, Minczuk M, Zsurka , Kunz WS

  • Tools such as mitoTALENs and mitochondrial ZFNs are able to cut mtDNA in a sequence-specific manner. Whilst these methods are known to be able to reduce the proportion of mutant mtDNAs, the mechanism by which linear mtDNAs are degraded is unknown.
  • The authors show that linear mtDNA is eliminated within hours
  • Inactivation of the mitochondrial exonuclease MGME1; inhibition of the exonuclease activity of POLG (see also this complementary study); or knockdown of the mitochondrial DNA helicase TWNK leads to severe imediment of mtDNA degradation. 
  • Failure to remove damaged mtDNA leads to the accumulation of abnormal linear and rearranged molecules.
  • Degradation of linearized mtDNA is performed by the same machinery that is responsible for mtDNA replication.

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