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

Author

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  • Nadee Nissanka

    (University of Miami Miller School of Medicine)

  • Sandra R. Bacman

    (University of Miami Miller School of Medicine)

  • Melanie J. Plastini

    (University of Miami Miller School of Medicine)

  • Carlos T. Moraes

    (University of Miami Miller School of Medicine
    University of Miami Miller School of Medicine)

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.

Suggested Citation

  • Nadee Nissanka & Sandra R. Bacman & Melanie J. Plastini & Carlos T. Moraes, 2018. "The mitochondrial DNA polymerase gamma degrades linear DNA fragments precluding the formation of deletions," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04895-1
    DOI: 10.1038/s41467-018-04895-1
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    Cited by:

    1. Julian C. W. Willis & Pedro Silva-Pinheiro & Lily Widdup & Michal Minczuk & David R. Liu, 2022. "Compact zinc finger base editors that edit mitochondrial or nuclear DNA in vitro and in vivo," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Liang Yang & Zifeng Ruan & Xiaobing Lin & Hao Wang & Yanmin Xin & Haite Tang & Zhijuan Hu & Yunhao Zhou & Yi Wu & Junwei Wang & Dajiang Qin & Gang Lu & Kerry M. Loomes & Wai-Yee Chan & Xingguo Liu, 2024. "NAD+ dependent UPRmt activation underlies intestinal aging caused by mitochondrial DNA mutations," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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