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Mol Cell Biol
1999 May 01;195:3869-76. doi: 10.1128/MCB.19.5.3869.
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The human DNA ligase III gene encodes nuclear and mitochondrial proteins.
Lakshmipathy U
,
Campbell C
.
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We provide evidence that the human DNA ligase III gene encodes a mitochondrial form of this enzyme. First, the DNA ligase III cDNA contains an in-frame ATG located upstream from the putative translation initiation start site. The DNA sequence between these two ATG sites encodes an amphipathic helix similar to previously identified mitochondrial targeting peptides. Second, recombinant green fluorescent protein harboring this sequence at its amino terminus was efficiently targeted to the mitochondria of Cos-1 monkey kidney cells. In contrast, native green fluorescent protein distributed to the cytosol. Third, a series of hemagglutinin-DNA ligase III minigene constructs were introduced into Cos-1 cells, and immunocytochemistry was used to determine subcellular localization of the epitope-tagged DNA ligase III protein. These experiments revealed that inactivation of the upstream ATG resulted in nuclear accumulation of the DNA ligase III protein, whereas inactivation of the downstream ATG abolished nuclear localization and led to accumulation within the mitochondrial compartment. Fourth, mitochondrial protein extracts prepared from human cells overexpressing antisense DNA ligase III mRNA possessed substantially less DNA ligase activity than did mitochondrial extracts prepared from control cells. DNA end-joining activity was also substantially reduced in extracts prepared from antisense mRNA-expressing cells. From these results, we conclude that the human DNA ligase III gene encodes both nuclear and mitochondrial enzymes. DNA ligase plays a central role in DNA replication, recombination, and DNA repair. Thus, identification of a mitochondrial form of this enzyme provides a tool with which to dissect mammalian mitochondrial genome dynamics.
Beltzer,
Yeast LEU4 encodes mitochondrial and nonmitochondrial forms of alpha-isopropylmalate synthase.
1988, Pubmed
Beltzer,
Yeast LEU4 encodes mitochondrial and nonmitochondrial forms of alpha-isopropylmalate synthase.
1988,
Pubmed
Brini,
Nuclear targeting of aequorin. A new approach for measuring nuclear Ca2+ concentration in intact cells.
1994,
Pubmed
Chen,
Mammalian DNA ligase III: molecular cloning, chromosomal localization, and expression in spermatocytes undergoing meiotic recombination.
1995,
Pubmed
,
Xenbase
Clayton,
The absence of a pyrimidine dimer repair mechanism in mammalian mitochondria.
1974,
Pubmed
Corral-Debrinski,
Marked changes in mitochondrial DNA deletion levels in Alzheimer brains.
1994,
Pubmed
Courchesne-Smith,
Cytoplasmic accumulation of a normally mitochondrial malonyl-CoA decarboxylase by the use of an alternate transcription start site.
1992,
Pubmed
Driggers,
Repair of oxidative damage within the mitochondrial DNA of RINr 38 cells.
1993,
Pubmed
Hamblet,
Elevated levels of the Kearns-Sayre syndrome mitochondrial DNA deletion in temporal cortex of Alzheimer's patients.
1997,
Pubmed
Horton,
Marked increase in mitochondrial DNA deletion levels in the cerebral cortex of Huntington's disease patients.
1995,
Pubmed
Keown,
Methods for introducing DNA into mammalian cells.
1990,
Pubmed
Kozak,
Interpreting cDNA sequences: some insights from studies on translation.
1996,
Pubmed
Kunkel,
Rapid and efficient site-specific mutagenesis without phenotypic selection.
1987,
Pubmed
Lakshmipathy,
Double strand break rejoining by mammalian mitochondrial extracts.
1999,
Pubmed
LeDoux,
Repair of mitochondrial DNA after various types of DNA damage in Chinese hamster ovary cells.
1992,
Pubmed
Levin,
A DNA ligase from mitochondria of rat liver.
1976,
Pubmed
Lopata,
High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment.
1984,
Pubmed
Miquel,
An update on the mitochondrial-DNA mutation hypothesis of cell aging.
1992,
Pubmed
Nagelhus,
Cell cycle regulation and subcellular localization of the major human uracil-DNA glycosylase.
1995,
Pubmed
North,
The rejoining of double-strand breaks in DNA by human cell extracts.
1990,
Pubmed
Pascucci,
DNA repair of UV photoproducts and mutagenesis in human mitochondrial DNA.
1997,
Pubmed
Pettepher,
Repair of alkali-labile sites within the mitochondrial DNA of RINr 38 cells after exposure to the nitrosourea streptozotocin.
1991,
Pubmed
Pinz,
Efficient repair of abasic sites in DNA by mitochondrial enzymes.
1998,
Pubmed
,
Xenbase
Rasheed,
Characterization of a newly derived human sarcoma cell line (HT-1080).
1974,
Pubmed
Reers,
J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential.
1991,
Pubmed
Rizzuto,
Chimeric green fluorescent protein as a tool for visualizing subcellular organelles in living cells.
1995,
Pubmed
Robins,
DNA ligase IV from HeLa cell nuclei.
1996,
Pubmed
,
Xenbase
Rost,
PHD--an automatic mail server for protein secondary structure prediction.
1994,
Pubmed
Rost,
Prediction of protein secondary structure at better than 70% accuracy.
1993,
Pubmed
Schiffer,
Use of helical wheels to represent the structures of proteins and to identify segments with helical potential.
1967,
Pubmed
Schneider,
Feature-extraction from endopeptidase cleavage sites in mitochondrial targeting peptides.
1998,
Pubmed
Shadel,
Mitochondrial DNA maintenance in vertebrates.
1997,
Pubmed
Shen,
Repair of mitochondrial DNA damage induced by bleomycin in human cells.
1995,
Pubmed
Slupphaug,
Nuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene.
1993,
Pubmed
Slusher,
mRNA leader length and initiation codon context determine alternative AUG selection for the yeast gene MOD5.
1991,
Pubmed
Snyderwine,
Gene- and strand-specific damage and repair in Chinese hamster ovary cells treated with 4-nitroquinoline 1-oxide.
1992,
Pubmed
Storrie,
Isolation of subcellular organelles.
1990,
Pubmed
Suomalainen,
An autosomal locus predisposing to deletions of mitochondrial DNA.
1995,
Pubmed
Suzuki,
Rat liver mitochondrial and cytosolic fumarases with identical amino acid sequences are encoded from a single gene.
1989,
Pubmed
Taffe,
Gene-specific nuclear and mitochondrial repair of formamidopyrimidine DNA glycosylase-sensitive sites in Chinese hamster ovary cells.
1996,
Pubmed
Thyagarajan,
Mammalian mitochondria possess homologous DNA recombination activity.
1996,
Pubmed
Tomkinson,
Mammalian DNA ligases.
1997,
Pubmed
Tomkinson,
Structure and function of mammalian DNA ligases.
1998,
Pubmed
Tomkinson,
Three distinct DNA ligases in mammalian cells.
1991,
Pubmed
,
Xenbase
Ueda,
Peroxisomal and mitochondrial carnitine acetyltransferase isozymes of the n-alkane-assimilating yeast, Candida tropicalis, occurred by alternative initiation of translation from the transcripts of a single gene.
1998,
Pubmed
von Heijne,
Mitochondrial targeting sequences may form amphiphilic helices.
1986,
Pubmed
von Heijne,
Domain structure of mitochondrial and chloroplast targeting peptides.
1989,
Pubmed
Wei,
Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination.
1995,
Pubmed
,
Xenbase
Zeviani,
Mitochondrial disorders.
1998,
Pubmed
