Molecular characterization of numr-1 and numr-2: genes that increase both resistance to metal-induced stress and lifespan in Caenorhabditis elegans

dc.contributor.author

Tvermoes, Brooke E

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Boyd, Windy A

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Freedman, Jonathan H

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2011-06-21T17:27:35Z

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2011-06-21T17:27:35Z

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2010

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To define the mechanisms involved in the molecular response to the carcinogenic metal cadmium, two novel metal-inducible genes from C. elegans were characterized: numr-1 and numr-2 (nuclear localized metal responsive). numr-1 and numr-2 sequences and cellular patterns of expression are identical, indicating that these are functionally equivalent genes. Constitutive transcription of numr-1 and numr-2 is developmentally regulated and occurs in the intestine, in head and tail neurons, and vulva muscles. Exposure to metals induces numr-1 and numr-2 transcription in pharyngeal and intestinal cells. Other environmental stressors do not affect transcription, indicating that these are metal-specific, stress-responsive genes. NUMR-1 and NUMR-2 target to nuclei and colocalize with HSF-1, suggesting that they may be components of nuclear stress granules. Nematodes overexpressing NUMR-1 and NUMR-2 are resistant to stress and live longer than control animals; likewise reducing expression increases sensitivity to metals and decreases neuromuscular functions. Upstream regulatory regions of both genes contain potential binding sites for DAF-16 and SKN-1, which are components of the insulin-IGF-like signaling pathway. This pathway regulates longevity and stress responses in C. elegans. NUMR-1 and NUMR-2 may function to promote resistance to environmental stressors and longevity, which is mediated by the insulin-IGF-like signaling pathway.

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Version of Record

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Tvermoes,Brooke E.;Boyd,Windy A.;Freedman,Jonathan H.. 2010. Molecular characterization of numr-1 and numr-2: genes that increase both resistance to metal-induced stress and lifespan in Caenorhabditis elegans. Journal of cell science 123(12): 2123-2133.

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0021-9533

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https://hdl.handle.net/10161/4187

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en_US

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The Company of Biologists

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10.1242/jcs.065433

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Journal of cell science

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c. elegans

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cadmium

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stress response

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lifespan

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longevity

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shock transcription factor-1

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unfolded protein response

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cell-specific

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expression

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c-elegans

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cadmium toxicity

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oxidative stress

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heavy-metal

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metallothionein genes

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regulatory elements

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signaling pathways

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cell biology

dc.title

Molecular characterization of numr-1 and numr-2: genes that increase both resistance to metal-induced stress and lifespan in Caenorhabditis elegans

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Other article

duke.date.pubdate

2010-6-15

duke.description.issue

12

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123

pubs.begin-page

2123

pubs.end-page

2133

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