DNA polymerase beta participates in mitochondrial DNA repair

P. Sykora, S. Kanno, M. Akbari, T. Kulikowicz, B. A. Baptiste, G. S. Leandro, Huiming Lu, J. Tian, A. May, K. A. Becker, D. L. Croteau, D. M. Wilson, R. W. Sobol, A. Yasui, V. A. Bohr

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

We have detected DNA polymerase beta (Polβ), known as a key nuclear base excision repair (BER) protein, in mitochondrial protein extracts derived from mammalian tissue and cells. Manipulation of the N-terminal sequence affected the amount of Polβ in the mitochondria. Using Polβ fragments, mitochondrion-specific protein partners were identified, with the interactors functioning mainly in DNA maintenance and mitochondrial import. Of particular interest was the identification of the proteins TWINKLE, SSBP1, and TFAM, all of which are mitochondrion-specific DNA effectors and are known to function in the nucleoid. Polβ directly interacted functionally with the mitochondrial helicase TWINKLE. Human kidney cells with Polβ knockout (KO) had higher endogenous mitochondrial DNA (mtDNA) damage. Mitochondrial extracts derived from heterozygous Polβ mouse tissue and KO cells had lower nucleotide incorporation activity. Mouse-derived Polβ null fibroblasts had severely affected metabolic parameters. Indeed, gene knockout of Polβ caused mitochondrial dysfunction, including reduced membrane potential and mitochondrial content. We show that Polβ is a mitochondrial polymerase involved in mtDNA maintenance and is required for mitochondrial homeostasis.

Original languageEnglish (US)
Article numbere00237-17
JournalMolecular and Cellular Biology
Volume37
Issue number16
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

Fingerprint

DNA Polymerase beta
Mitochondrial DNA
DNA Repair
Mitochondria
Maintenance
Gene Knockout Techniques
Proteins
Mitochondrial Membrane Potential
Mitochondrial Proteins
Knockout Mice
DNA Damage
Homeostasis
Nucleotides
Fibroblasts
Kidney
DNA

Keywords

  • Base excision repair
  • DNA polymerase beta
  • Mitochondria
  • Mitochondrial DNA repair
  • Mitochondrial health
  • Mutational studies
  • TFAM

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Sykora, P., Kanno, S., Akbari, M., Kulikowicz, T., Baptiste, B. A., Leandro, G. S., ... Bohr, V. A. (2017). DNA polymerase beta participates in mitochondrial DNA repair. Molecular and Cellular Biology, 37(16), [e00237-17]. https://doi.org/10.1128/MCB.00237-17

DNA polymerase beta participates in mitochondrial DNA repair. / Sykora, P.; Kanno, S.; Akbari, M.; Kulikowicz, T.; Baptiste, B. A.; Leandro, G. S.; Lu, Huiming; Tian, J.; May, A.; Becker, K. A.; Croteau, D. L.; Wilson, D. M.; Sobol, R. W.; Yasui, A.; Bohr, V. A.

In: Molecular and Cellular Biology, Vol. 37, No. 16, e00237-17, 01.08.2017.

Research output: Contribution to journalArticle

Sykora, P, Kanno, S, Akbari, M, Kulikowicz, T, Baptiste, BA, Leandro, GS, Lu, H, Tian, J, May, A, Becker, KA, Croteau, DL, Wilson, DM, Sobol, RW, Yasui, A & Bohr, VA 2017, 'DNA polymerase beta participates in mitochondrial DNA repair', Molecular and Cellular Biology, vol. 37, no. 16, e00237-17. https://doi.org/10.1128/MCB.00237-17
Sykora P, Kanno S, Akbari M, Kulikowicz T, Baptiste BA, Leandro GS et al. DNA polymerase beta participates in mitochondrial DNA repair. Molecular and Cellular Biology. 2017 Aug 1;37(16). e00237-17. https://doi.org/10.1128/MCB.00237-17
Sykora, P. ; Kanno, S. ; Akbari, M. ; Kulikowicz, T. ; Baptiste, B. A. ; Leandro, G. S. ; Lu, Huiming ; Tian, J. ; May, A. ; Becker, K. A. ; Croteau, D. L. ; Wilson, D. M. ; Sobol, R. W. ; Yasui, A. ; Bohr, V. A. / DNA polymerase beta participates in mitochondrial DNA repair. In: Molecular and Cellular Biology. 2017 ; Vol. 37, No. 16.
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