Copy-choice recombination during mitochondrial L-strand synthesis causes DNA deletions
| Autor: | Persson, Örjan, Muthukumar, Yazh, Basu, Swaraj, Jenninger, Louise, Uhler, Jay P., Berglund, Anna-Karin, McFarland, Robert, Taylor, Robert W., Gustafsson, Claes M., Larsson, Erik, Falkenberg, Maria |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-10 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Mitochondrial DNA (mtDNA) deletions are associated with mitochondrial disease, and also accumulate during normal human ageing. The mechanisms underlying mtDNA deletions remain unknown although several models have been proposed. Here we use deep sequencing to characterize abundant mtDNA deletions in patients with mutations in mitochondrial DNA replication factors, and show that these have distinct directionality and repeat characteristics. Furthermore, we recreate the deletion formation process in vitro using only purified mitochondrial proteins and defined DNA templates. Based on our in vivo and in vitro findings, we conclude that mtDNA deletion formation involves copy-choice recombination during replication of the mtDNA light strand. Large-scale deletions of mitochondrial DNA (mtDNA) are associated with different human mitochondrial diseases and normal human ageing. Here the authors present a model for mtDNA formation based on generation sequencing analysis of patients samples and in vitro reconstituted mtDNA deletion using purified proteins. |
| Databáze: | OpenAIRE |
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