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Proc Natl Acad Sci U S A
2010 Nov 16;10746:19790-5. doi: 10.1073/pnas.1009814107.
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Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria.
Das BB, Dexheimer TS, Maddali K, Pommier Y.
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Human tyrosyl-DNA phosphodiesterase (TDP1) hydrolyzes the phosphodiester bond at a DNA 3'-end linked to a tyrosyl moiety and has been implicated in the repair of topoisomerase I (Top1)-DNA covalent complexes. TDP1 can also hydrolyze other 3'-end DNA alterations including 3'-phosphoglycolate and 3'-abasic sites, and exhibits 3'-nucleosidase activity indicating it may function as a general 3'-end-processing DNA repair enzyme. Here, using laser confocal microscopy, subcellular fractionation and biochemical analyses we demonstrate that a fraction of the TDP1 encoded by the nuclear TDP1 gene localizes to mitochondria. We also show that mitochondrial base excision repair depends on TDP1 activity and provide evidence that TDP1 is required for efficient repair of oxidative damage in mitochondrial DNA. Together, our findings provide evidence for TDP1 as a novel mitochondrial enzyme.
Bacman,
Intra- and inter-molecular recombination of mitochondrial DNA after in vivo induction of multiple double-strand breaks.
2009, Pubmed
Bacman,
Intra- and inter-molecular recombination of mitochondrial DNA after in vivo induction of multiple double-strand breaks.
2009,
Pubmed Ben Hassine,
Tdp1 protects against oxidative DNA damage in non-dividing fission yeast.
2009,
Pubmed Bogenhagen,
The number of mitochondrial deoxyribonucleic acid genomes in mouse L and human HeLa cells. Quantitative isolation of mitochondrial deoxyribonucleic acid.
1974,
Pubmed Bogenhagen,
Repair of mtDNA in vertebrates.
1999,
Pubmed Bogenhagen,
Enzymology of mitochondrial base excision repair.
2001,
Pubmed
,
Xenbase Bolender,
Multiple pathways for sorting mitochondrial precursor proteins.
2008,
Pubmed Bonawitz,
Initiation and beyond: multiple functions of the human mitochondrial transcription machinery.
2006,
Pubmed Champoux,
DNA topoisomerases: structure, function, and mechanism.
2001,
Pubmed Chattopadhyay,
Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells.
2006,
Pubmed Chaudhry,
Removal by human apurinic/apyrimidinic endonuclease 1 (Ape 1) and Escherichia coli exonuclease III of 3'-phosphoglycolates from DNA treated with neocarzinostatin, calicheamicin, and gamma-radiation.
1999,
Pubmed Chen,
Two distinct human DNA diesterases that hydrolyze 3'-blocking deoxyribose fragments from oxidized DNA.
1991,
Pubmed Chen,
Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations.
2010,
Pubmed Coffey,
An alternate form of Ku80 is required for DNA end-binding activity in mammalian mitochondria.
2000,
Pubmed Copeland,
DNA2 resolves expanding flap in mitochondrial base excision repair.
2008,
Pubmed Daroui,
Hydrogen peroxide induces topoisomerase I-mediated DNA damage and cell death.
2004,
Pubmed Das,
Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK.
2009,
Pubmed Debéthune,
Processing of nucleopeptides mimicking the topoisomerase I-DNA covalent complex by tyrosyl-DNA phosphodiesterase.
2002,
Pubmed Demple,
Repair of oxidative damage to DNA: enzymology and biology.
1994,
Pubmed de Souza-Pinto,
Novel DNA mismatch-repair activity involving YB-1 in human mitochondria.
2009,
Pubmed de Souza-Pinto,
Mitochondrial DNA, base excision repair and neurodegeneration.
2008,
Pubmed Dexheimer,
Tyrosyl-DNA phosphodiesterase as a target for anticancer therapy.
2008,
Pubmed El-Khamisy,
Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1.
2005,
Pubmed
,
Xenbase El-Khamisy,
TDP1 facilitates repair of ionizing radiation-induced DNA single-strand breaks.
2007,
Pubmed Fisher,
Purification and characterization of human mitochondrial transcription factor 1.
1988,
Pubmed Hadi,
Determinants in nuclease specificity of Ape1 and Ape2, human homologues of Escherichia coli exonuclease III.
2002,
Pubmed Hawkins,
In vitro complementation of Tdp1 deficiency indicates a stabilized enzyme-DNA adduct from tyrosyl but not glycolate lesions as a consequence of the SCAN1 mutation.
2009,
Pubmed Hirano,
Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation?
2007,
Pubmed Holt,
Mitochondrial DNA replication and repair: all a flap.
2009,
Pubmed Inamdar,
Conversion of phosphoglycolate to phosphate termini on 3' overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1.
2002,
Pubmed Interthal,
Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages.
2005,
Pubmed Interthal,
The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D superfamily.
2001,
Pubmed Izumi,
Requirement for human AP endonuclease 1 for repair of 3'-blocking damage at DNA single-strand breaks induced by reactive oxygen species.
2000,
Pubmed Kaguni,
DNA polymerase gamma, the mitochondrial replicase.
2004,
Pubmed Katyal,
TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo.
2007,
Pubmed Lakshmipathy,
The human DNA ligase III gene encodes nuclear and mitochondrial proteins.
1999,
Pubmed
,
Xenbase Li,
Identification and characterization of mitochondrial targeting sequence of human apurinic/apyrimidinic endonuclease 1.
2010,
Pubmed Marchenko,
Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling.
2000,
Pubmed Miao,
Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes.
2006,
Pubmed Nitiss,
Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage.
2006,
Pubmed Parsons,
APE1 is the major 3'-phosphoglycolate activity in human cell extracts.
2004,
Pubmed Pinz,
Efficient repair of abasic sites in DNA by mitochondrial enzymes.
1998,
Pubmed
,
Xenbase Pommier,
Repair of topoisomerase I-mediated DNA damage.
2006,
Pubmed Pouliot,
Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes.
1999,
Pubmed Pourquier,
Topoisomerase I-mediated DNA damage.
2001,
Pubmed Pourquier,
Induction of reversible complexes between eukaryotic DNA topoisomerase I and DNA-containing oxidative base damages. 7, 8-dihydro-8-oxoguanine and 5-hydroxycytosine.
1999,
Pubmed Psarra,
Nuclear receptors and other nuclear transcription factors in mitochondria: regulatory molecules in a new environment.
2008,
Pubmed Richter,
Normal oxidative damage to mitochondrial and nuclear DNA is extensive.
1988,
Pubmed Sage,
Discovery of a novel function for human Rad51: maintenance of the mitochondrial genome.
2010,
Pubmed Santos,
Quantitative PCR-based measurement of nuclear and mitochondrial DNA damage and repair in mammalian cells.
2006,
Pubmed Suh,
3'-phosphodiesterase activity of human apurinic/apyrimidinic endonuclease at DNA double-strand break ends.
1997,
Pubmed Szczesny,
Long patch base excision repair in mammalian mitochondrial genomes.
2008,
Pubmed Takashima,
Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy.
2002,
Pubmed Thyagarajan,
Mammalian mitochondria possess homologous DNA recombination activity.
1996,
Pubmed Tsuchimoto,
Human APE2 protein is mostly localized in the nuclei and to some extent in the mitochondria, while nuclear APE2 is partly associated with proliferating cell nuclear antigen.
2001,
Pubmed Wallace,
A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine.
2005,
Pubmed Wilson,
Processing of nonconventional DNA strand break ends.
2007,
Pubmed Winters,
Determination of human DNA polymerase utilization for the repair of a model ionizing radiation-induced DNA strand break lesion in a defined vector substrate.
1999,
Pubmed
,
Xenbase Yakes,
Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress.
1997,
Pubmed Yang,
A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases.
1996,
Pubmed Zhang,
Human mitochondrial topoisomerase I.
2001,
Pubmed Zhang,
Mitochondrial topoisomerase I sites in the regulatory D-loop region of mitochondrial DNA.
2008,
Pubmed Zheng,
Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates.
2008,
Pubmed Zhou,
Deficiency in 3'-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1).
2005,
Pubmed Zhou,
Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks.
2009,
Pubmed
