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REC drives recombination to repair double-strand breaks in animal mtDNA

Anna Klucnika1,2, Peiqiang Mu1,2,3, Jan Jezek1,2

  • 1Wellcome/Cancer Research UK Gurdon Institute, Cambridge, UK.

The Journal of Cell Biology
|November 10, 2022
PubMed

Insights

Mitochondrial DNA (mtDNA) double-strand breaks are repaired by REC, a helicase found in Drosophila mitochondria. This discovery reveals a new pathway for mtDNA repair, crucial for preventing age-related mutations and maintaining genome stability.

Area of Science:

  • Mitochondrial biology and genetics
  • DNA repair mechanisms
  • Aging research

Background:

  • Mitochondrial DNA (mtDNA) integrity is vital for preventing mitochondrial and age-related diseases.
  • Pathways for repairing double-strand breaks (DSBs) within animal mitochondria remain largely uncharacterized.

Purpose of the Study:

  • To identify proteins involved in mitochondrial DNA repair.
  • To elucidate the mechanisms of mtDNA double-strand break repair in animals.
  • To investigate the role of identified repair pathways in preventing age-associated mtDNA mutations.

Main Methods:

  • Candidate screening for mitochondrial DNA repair proteins in Drosophila.
  • Localization studies of the MCM helicase REC in Drosophila.
  • Functional assays to assess REC's role in repairing mtDNA DSBs via homologous recombination.
  • Analysis of age-associated mtDNA mutations in the presence and absence of REC.
  • Comparative studies using the human ortholog, MCM8.

Main Results:

  • The MCM helicase REC was identified and localized to mitochondria in Drosophila.
  • REC was shown to repair mtDNA DSBs through homologous recombination in both somatic and germline cells.
  • REC activity was found to prevent the accumulation of age-associated mtDNA mutations.
  • The human ortholog, MCM8, also localizes to mitochondria and limits mtDNA mutations.

Conclusions:

  • This study reveals a novel mechanism for animal mtDNA double-strand break repair involving the MCM helicase REC.
  • Mitochondrial DNA recombination is crucial for safeguarding mtDNA integrity during aging.
  • The findings highlight the evolutionary importance of mtDNA repair mechanisms in preventing disease and promoting longevity.

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