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rdf:type |
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lifeskim:mentions |
umls-concept:C0007587,
umls-concept:C0012854,
umls-concept:C0015296,
umls-concept:C0036849,
umls-concept:C0439855,
umls-concept:C0812204,
umls-concept:C1333877,
umls-concept:C1336670,
umls-concept:C1366517,
umls-concept:C1442518,
umls-concept:C1551336,
umls-concept:C1552652,
umls-concept:C1552685,
umls-concept:C1705195,
umls-concept:C1709130
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pubmed:issue |
1
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pubmed:dateCreated |
2006-7-4
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pubmed:abstractText |
Granzyme A (GzmA) activates a caspase-independent cell death pathway with morphological features of apoptosis. Single-stranded DNA damage is initiated when the endonuclease NM23-H1 becomes activated to nick DNA after granzyme A cleaves its inhibitor, SET. SET and NM23-H1 reside in an endoplasmic reticulum-associated complex (the SET complex) that translocates to the nucleus in response to superoxide generation by granzyme A. We now find the 3'-to-5' exonuclease TREX1, but not its close homolog TREX2, in the SET complex. TREX1 binds to SET and colocalizes and translocates with the SET complex. NM23-H1 and TREX1 work in concert to degrade DNA. Silencing NM23-H1 or TREX1 inhibits DNA damage and death of cells treated with perforin (PFN) and granzyme A, but not of cells treated with perforin and granzyme B (GzmB). After granzyme A activates NM23-H1 to make single-stranded nicks, TREX1 removes nucleotides from the nicked 3' end to reduce the possibility of repair by rejoining the nicked ends.
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pubmed:grant |
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Exodeoxyribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/GZMA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Granzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/NM23 Nucleoside Diphosphate Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NME1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleoside-Diphosphate Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/three prime repair exonuclease 1
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
133-42
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16818237-Cell Death,
pubmed-meshheading:16818237-Cell Line, Tumor,
pubmed-meshheading:16818237-DNA,
pubmed-meshheading:16818237-DNA Damage,
pubmed-meshheading:16818237-Exodeoxyribonucleases,
pubmed-meshheading:16818237-Gene Silencing,
pubmed-meshheading:16818237-Granzymes,
pubmed-meshheading:16818237-HeLa Cells,
pubmed-meshheading:16818237-Humans,
pubmed-meshheading:16818237-K562 Cells,
pubmed-meshheading:16818237-Multienzyme Complexes,
pubmed-meshheading:16818237-NM23 Nucleoside Diphosphate Kinases,
pubmed-meshheading:16818237-Nucleoside-Diphosphate Kinase,
pubmed-meshheading:16818237-Phosphoproteins,
pubmed-meshheading:16818237-Serine Endopeptidases,
pubmed-meshheading:16818237-Substrate Specificity
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pubmed:year |
2006
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pubmed:articleTitle |
The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death.
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pubmed:affiliation |
CBR Institute for Biomedical Research, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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