Source:http://linkedlifedata.com/resource/pubmed/id/20854421
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2010-11-12
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pubmed:abstractText |
Conserved metallo ?-Lactamase and ?-CASP (CPSF-Artemis-Snm1-Pso2) domain nuclease family member SNM1B/Apollo is a shelterin-associated protein that localizes to telomeres through its interaction with TRF2. To study its in vivo role, we generated a knockout of SNM1B/Apollo in a mouse model. Snm1B/Apollo homozygous null mice die at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Snm1B/Apollo mutant mouse embryonic fibroblasts (MEFs) owing to high levels of telomeric end-to-end fusions. Deficiency of the nonhomologous end-joining (NHEJ) factor Ku70, but not p53, rescued the developmental defects and lethality observed in Snm1B/Apollo mutant mice as well as the impaired proliferation of Snm1B/Apollo-deficient MEFs. These findings demonstrate that SNM1B/Apollo is required to protect telomeres against NHEJ-mediated repair, which results in genomic instability and the consequent multi-organ developmental failure. Although Snm1B/Apollo-deficient MEFs exhibited high levels of apoptosis, abrogation of p53-dependent programmed cell death did not rescue the multi-organ developmental failure in the mice.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dclre1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Telomere-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1474-9726
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pubmed:author | |
pubmed:copyrightInfo |
© 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
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pubmed:issnType |
Electronic
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1047-56
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pubmed:meshHeading |
pubmed-meshheading:20854421-Animals,
pubmed-meshheading:20854421-Apoptosis,
pubmed-meshheading:20854421-Cell Cycle Proteins,
pubmed-meshheading:20854421-Cell Proliferation,
pubmed-meshheading:20854421-Embryo, Mammalian,
pubmed-meshheading:20854421-Embryonic Development,
pubmed-meshheading:20854421-Female,
pubmed-meshheading:20854421-Genomic Instability,
pubmed-meshheading:20854421-Mice,
pubmed-meshheading:20854421-Mice, Knockout,
pubmed-meshheading:20854421-Pregnancy,
pubmed-meshheading:20854421-Telomere,
pubmed-meshheading:20854421-Telomere-Binding Proteins,
pubmed-meshheading:20854421-Tumor Suppressor Protein p53
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pubmed:year |
2010
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pubmed:articleTitle |
The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development.
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pubmed:affiliation |
Department of Genetics, The UT MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, 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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