Slow mitochondrial repair of 5'-AMP renders mtDNA susceptible to damage in APTX deficient cells

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Slow mitochondrial repair of 5'-AMP renders mtDNA susceptible to damage in APTX deficient cells. / Akbari, Mansour; Sykora, Peter; Bohr, Vilhelm A.

In: Scientific Reports, Vol. 5, 12876 , 10.08.2015.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Akbari, M, Sykora, P & Bohr, VA 2015, 'Slow mitochondrial repair of 5'-AMP renders mtDNA susceptible to damage in APTX deficient cells', Scientific Reports, vol. 5, 12876 . https://doi.org/10.1038/srep12876

APA

Akbari, M., Sykora, P., & Bohr, V. A. (2015). Slow mitochondrial repair of 5'-AMP renders mtDNA susceptible to damage in APTX deficient cells. Scientific Reports, 5, [12876 ]. https://doi.org/10.1038/srep12876

Vancouver

Akbari M, Sykora P, Bohr VA. Slow mitochondrial repair of 5'-AMP renders mtDNA susceptible to damage in APTX deficient cells. Scientific Reports. 2015 Aug 10;5. 12876 . https://doi.org/10.1038/srep12876

Author

Akbari, Mansour ; Sykora, Peter ; Bohr, Vilhelm A. / Slow mitochondrial repair of 5'-AMP renders mtDNA susceptible to damage in APTX deficient cells. In: Scientific Reports. 2015 ; Vol. 5.

Bibtex

@article{dcc359b3565340019e1e22bcc671bf65,
title = "Slow mitochondrial repair of 5'-AMP renders mtDNA susceptible to damage in APTX deficient cells",
abstract = "Aborted DNA ligation events in eukaryotic cells can generate 5'-adenylated (5'-AMP) DNA termini that can be removed from DNA by aprataxin (APTX). Mutations in APTX cause an inherited human disease syndrome characterized by early-onset progressive ataxia with ocular motor apraxia (AOA1). APTX is found in the nuclei and mitochondria of eukaryotic cells. Depletion of APTX causes mitochondrial dysfunction and renders the mitochondrial genome, but not the nuclear genome susceptible to damage. The biochemical processes that link APTX deficiency to mitochondrial dysfunction have not been well elucidated. Here, we monitored the repair of 5'-AMP DNA damage in nuclear and mitochondrial extracts from human APTX(+/+) and APTX(-/-) cells. The efficiency of repair of 5'-AMP DNA was much lower in mitochondrial than in nuclear protein extracts, and resulted in persistent DNA repair intermediates in APTX deficient cells. Moreover, the removal of 5'-AMP from DNA was significantly slower in the mitochondrial extracts from human cell lines and mouse tissues compared with their corresponding nuclear extracts. These results suggest that, contrary to nuclear DNA repair, mitochondrial DNA repair is not able to compensate for APTX deficiency resulting in the accumulation of mitochondrial DNA damage.",
author = "Mansour Akbari and Peter Sykora and Bohr, {Vilhelm A}",
year = "2015",
month = "8",
day = "10",
doi = "10.1038/srep12876",
language = "English",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Slow mitochondrial repair of 5'-AMP renders mtDNA susceptible to damage in APTX deficient cells

AU - Akbari, Mansour

AU - Sykora, Peter

AU - Bohr, Vilhelm A

PY - 2015/8/10

Y1 - 2015/8/10

N2 - Aborted DNA ligation events in eukaryotic cells can generate 5'-adenylated (5'-AMP) DNA termini that can be removed from DNA by aprataxin (APTX). Mutations in APTX cause an inherited human disease syndrome characterized by early-onset progressive ataxia with ocular motor apraxia (AOA1). APTX is found in the nuclei and mitochondria of eukaryotic cells. Depletion of APTX causes mitochondrial dysfunction and renders the mitochondrial genome, but not the nuclear genome susceptible to damage. The biochemical processes that link APTX deficiency to mitochondrial dysfunction have not been well elucidated. Here, we monitored the repair of 5'-AMP DNA damage in nuclear and mitochondrial extracts from human APTX(+/+) and APTX(-/-) cells. The efficiency of repair of 5'-AMP DNA was much lower in mitochondrial than in nuclear protein extracts, and resulted in persistent DNA repair intermediates in APTX deficient cells. Moreover, the removal of 5'-AMP from DNA was significantly slower in the mitochondrial extracts from human cell lines and mouse tissues compared with their corresponding nuclear extracts. These results suggest that, contrary to nuclear DNA repair, mitochondrial DNA repair is not able to compensate for APTX deficiency resulting in the accumulation of mitochondrial DNA damage.

AB - Aborted DNA ligation events in eukaryotic cells can generate 5'-adenylated (5'-AMP) DNA termini that can be removed from DNA by aprataxin (APTX). Mutations in APTX cause an inherited human disease syndrome characterized by early-onset progressive ataxia with ocular motor apraxia (AOA1). APTX is found in the nuclei and mitochondria of eukaryotic cells. Depletion of APTX causes mitochondrial dysfunction and renders the mitochondrial genome, but not the nuclear genome susceptible to damage. The biochemical processes that link APTX deficiency to mitochondrial dysfunction have not been well elucidated. Here, we monitored the repair of 5'-AMP DNA damage in nuclear and mitochondrial extracts from human APTX(+/+) and APTX(-/-) cells. The efficiency of repair of 5'-AMP DNA was much lower in mitochondrial than in nuclear protein extracts, and resulted in persistent DNA repair intermediates in APTX deficient cells. Moreover, the removal of 5'-AMP from DNA was significantly slower in the mitochondrial extracts from human cell lines and mouse tissues compared with their corresponding nuclear extracts. These results suggest that, contrary to nuclear DNA repair, mitochondrial DNA repair is not able to compensate for APTX deficiency resulting in the accumulation of mitochondrial DNA damage.

U2 - 10.1038/srep12876

DO - 10.1038/srep12876

M3 - Journal article

VL - 5

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 12876

ER -

ID: 143667346