Complementation between polymerase- and exonuclease-deficient mitochondrial DNA polymerase mutants in genomically engineered flies

Ana Bratic, Timo E. S. Kauppila, Bertil Macao, Sebastian Grönke, Triinu Siibak, James B. Stewart, Francesca Baggio, Jacqueline Dols, Linda Partridge, Maria Falkenberg, Anna Wredenberg () and Nils-Göran Larsson ()
Additional contact information
Ana Bratic: Max Planck Institute for Biology of Ageing
Timo E. S. Kauppila: Max Planck Institute for Biology of Ageing
Bertil Macao: Institute of Biomedicine, University of Gothenburg, Medicinaregatan 9A
Sebastian Grönke: Max Planck Institute for Biology of Ageing
Triinu Siibak: Institute of Biomedicine, University of Gothenburg, Medicinaregatan 9A
James B. Stewart: Max Planck Institute for Biology of Ageing
Francesca Baggio: Max Planck Institute for Biology of Ageing
Jacqueline Dols: Max Planck Institute for Biology of Ageing
Linda Partridge: Max Planck Institute for Biology of Ageing
Maria Falkenberg: Institute of Biomedicine, University of Gothenburg, Medicinaregatan 9A
Anna Wredenberg: Karolinska Institutet
Nils-Göran Larsson: Max Planck Institute for Biology of Ageing

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract Replication errors are the main cause of mitochondrial DNA (mtDNA) mutations and a compelling approach to decrease mutation levels would therefore be to increase the fidelity of the catalytic subunit (POLγA) of the mtDNA polymerase. Here we genomically engineer the tamas locus, encoding fly POLγA, and introduce alleles expressing exonuclease- (exo−) and polymerase-deficient (pol−) POLγA versions. The exo− mutant leads to accumulation of point mutations and linear deletions of mtDNA, whereas pol− mutants cause mtDNA depletion. The mutant tamas alleles are developmentally lethal but can complement each other in trans resulting in viable flies with clonally expanded mtDNA mutations. Reconstitution of human mtDNA replication in vitro confirms that replication is a highly dynamic process where POLγA goes on and off the template to allow complementation during proofreading and elongation. The created fly models are valuable tools to study germ line transmission of mtDNA and the pathophysiology of POLγA mutation disease.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/ncomms9808 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9808

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9808

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().