DNA Polymerase Beta Participates in Mitochondrial DNA Repair.

Autor:	Sykora P; Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA.; Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA., Kanno S; Division of Dynamic Proteome in Cancer and Aging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan., Akbari M; Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark., Kulikowicz T; Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA., Baptiste BA; Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA., Leandro GS; Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA.; Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil., Lu H; Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA., Tian J; Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA., May A; Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA., Becker KA; Laboratory of Genetics, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA., Croteau DL; Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA., Wilson DM 3rd; Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA., Sobol RW; Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA., Yasui A; Division of Dynamic Proteome in Cancer and Aging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan., Bohr VA; Laboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USA BohrV@grc.nia.nih.gov.
Jazyk:	angličtina
Zdroj:	Molecular and cellular biology [Mol Cell Biol] 2017 Jul 28; Vol. 37 (16). Date of Electronic Publication: 2017 Jul 28 (Print Publication: 2017).
DOI:	10.1128/MCB.00237-17
Abstrakt:	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. (Copyright © 2017 American Society for Microbiology.)
Databáze:	MEDLINE
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