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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2000-8-24
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pubmed:databankReference |
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pubmed:abstractText |
Three cytosolic and one plasma membrane-bound 5'-nucleotidases have been cloned and characterized. Their various substrate specificities suggest widely different functions in nucleotide metabolism. We now describe a 5'-nucleotidase in mitochondria. The enzyme, named dNT-2, dephosphorylates specifically the 5'- and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides. The cDNA of human dNT-2 codes for a 25.9-kDa polypeptide with a typical mitochondrial leader peptide, providing the structural basis for two-step processing during import into the mitochondrial matrix. The deduced amino acid sequence is 52% identical to that of a recently described cytosolic deoxyribonucleotidase (dNT-1). The two enzymes share many catalytic properties, but dNT-2 shows a narrower substrate specificity. Mitochondrial localization of dNT-2 was demonstrated by the mitochondrial fluorescence of 293 cells expressing a dNT-2-green fluorescent protein (GFP) fusion protein. 293 cells expressing fusion proteins without leader peptide or with dNT-1 showed a cytosolic fluorescence. During in vitro import into mitochondria, the preprotein lost the leader peptide. We suggest that dNT-2 protects mitochondrial DNA replication from overproduction of dTTP, in particular in resting cells. Mitochondrial toxicity of dTTP can be inferred from a severe inborn error of metabolism in which the loss of thymidine phosphorylase led to dTTP accumulation and aberrant mitochondrial DNA replication. We localized the gene for dNT-2 on chromosome 17p11.2 in the Smith-Magenis syndrome-critical region, raising the possibility that dNT-2 is involved in the etiology of this genetic disease.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-10191102,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-10585270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-10681516,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-10976232,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-1637327,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-1943808,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-2425619,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-272665,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-2837322,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-3052277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-3894352,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-4117384,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-4735344,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-48676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-6213605,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-6256438,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-7519315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-7593000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-8206987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-8622939,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-8692979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-8706825,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-9006939,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-9242927,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-96138,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-9759496,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-9924029,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-9988697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-9988709,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10899995-9989599
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8239-44
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10899995-5'-Nucleotidase,
pubmed-meshheading:10899995-Abnormalities, Multiple,
pubmed-meshheading:10899995-Amino Acid Sequence,
pubmed-meshheading:10899995-Animals,
pubmed-meshheading:10899995-Base Sequence,
pubmed-meshheading:10899995-Brain,
pubmed-meshheading:10899995-Cell Line,
pubmed-meshheading:10899995-DNA, Complementary,
pubmed-meshheading:10899995-Deoxyuracil Nucleotides,
pubmed-meshheading:10899995-Genetic Diseases, Inborn,
pubmed-meshheading:10899995-Humans,
pubmed-meshheading:10899995-Mice,
pubmed-meshheading:10899995-Mitochondria, Muscle,
pubmed-meshheading:10899995-Molecular Sequence Data,
pubmed-meshheading:10899995-Myocardium,
pubmed-meshheading:10899995-Nucleotides,
pubmed-meshheading:10899995-Purine-Pyrimidine Metabolism, Inborn Errors,
pubmed-meshheading:10899995-Rats,
pubmed-meshheading:10899995-Substrate Specificity,
pubmed-meshheading:10899995-Thymidine Monophosphate,
pubmed-meshheading:10899995-Tissue Distribution
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pubmed:year |
2000
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pubmed:articleTitle |
A deoxyribonucleotidase in mitochondria: involvement in regulation of dNTP pools and possible link to genetic disease.
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pubmed:affiliation |
Departments of Biology and Biomedical Sciences, University of Padua, I-35131 Padua, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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