DNA polymerase beta participates in mitochondrial DNA repair
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DNA polymerase beta participates in mitochondrial DNA repair. / Sykora, P; Kanno, S; Akbari, M; Kulikowicz, T; Baptiste, B A; Leandro, G S; Lu, H; 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, 08.2017.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - DNA polymerase beta participates in mitochondrial DNA repair
AU - Sykora, P
AU - Kanno, S
AU - Akbari, M
AU - Kulikowicz, T
AU - Baptiste, B A
AU - Leandro, G S
AU - Lu, H
AU - Tian, J
AU - May, A
AU - Becker, K A
AU - Croteau, D L
AU - Wilson, D M
AU - Sobol, R W
AU - Yasui, A
AU - Bohr, V A
N1 - Copyright © 2017 American Society for Microbiology.
PY - 2017/8
Y1 - 2017/8
N2 - 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, mitochondrial-specific protein partners were identified, with the interactors mainly functioning in DNA maintenance and mitochondrial import. Of particular interest was the identification of the proteins TWINKLE, SSBP1 and TFAM, all of which are mitochondria specific DNA effectors and are known to function in the nucleoid. Polβ directly interacted with, and influenced the activity of, the mitochondrial helicase TWINKLE. Human kidney cells with Polβ knock-out (KO) had higher endogenous 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.
AB - 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, mitochondrial-specific protein partners were identified, with the interactors mainly functioning in DNA maintenance and mitochondrial import. Of particular interest was the identification of the proteins TWINKLE, SSBP1 and TFAM, all of which are mitochondria specific DNA effectors and are known to function in the nucleoid. Polβ directly interacted with, and influenced the activity of, the mitochondrial helicase TWINKLE. Human kidney cells with Polβ knock-out (KO) had higher endogenous 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.
U2 - 10.1128/MCB.00237-17
DO - 10.1128/MCB.00237-17
M3 - Journal article
C2 - 28559431
VL - 37
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 16
M1 - e00237-17
ER -
ID: 185901118