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What causes mitochondrial DNA deletions in human cells?


Mitochondrial DNA (mtDNA) deletions are a primary cause of mitochondrial disease and are likely to have a central role in the aging of postmitotic tissues. Understanding the mechanism of the formation and subsequent clonal expansion of these mtDNA deletions is an essential first step in trying to prevent their occurrence. We review the previous literature and recent results from our own laboratories, and conclude that mtDNA deletions are most likely to occur during repair of damaged mtDNA rather than during replication. This conclusion has important implications for prevention of mtDNA disease and, potentially, for our understanding of the aging process.

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Figure 1: Diagram illustrating the proposed methods of mtDNA replication.
Figure 2: Diagram illustrating the previously proposed formation of an mtDNA deletion through a slipped-strand model of replication.
Figure 3
Figure 4: A simplified diagram of our proposed model for the generation of mtDNA deletions during repair of DSBs.
Figure 5: Proposed model showing how sporadic mtDNA deletions occur in the oocyte.


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We wish to acknowledge financial support from the Alzheimer's Research Trust, the Wellcome Trust, EUMitocombat and the Medical Research Council.

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Krishnan, K., Reeve, A., Samuels, D. et al. What causes mitochondrial DNA deletions in human cells?. Nat Genet 40, 275–279 (2008).

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