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Nat Commun. 2018 Jun 27;9(1):2491. doi: 10.1038/s41467-018-04895-1.

The mitochondrial DNA polymerase gamma degrades linear DNA fragments precluding the formation of deletions.

Author information

1
Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
2
Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
3
Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. cmoraes@med.miami.edu.
4
Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. cmoraes@med.miami.edu.

Abstract

Double-strand breaks in the mitochondrial DNA (mtDNA) result in the formation of linear fragments that are rapidly degraded. However, the identity of the nuclease(s) performing this function is not known. We found that the exonuclease function of the mtDNA polymerase gamma (POLG) is required for this rapid degradation of mtDNA fragments. POLG is recruited to linearized DNA fragments in an origin of replication-independent manner. Moreover, in the absence of POLG exonuclease activity, the prolonged existence of mtDNA linear fragments leads to increased levels of mtDNA deletions, which have been previously identified in the mutator mouse, patients with POLG mutations and normal aging.

PMID:
29950568
PMCID:
PMC6021392
DOI:
10.1038/s41467-018-04895-1
[Indexed for MEDLINE]
Free PMC Article

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