Source:http://linkedlifedata.com/resource/pubmed/id/11889123
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
21
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pubmed:dateCreated |
2002-5-20
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pubmed:abstractText |
Human Werner Syndrome is characterized by early onset of aging, elevated chromosomal instability, and a high incidence of cancer. Werner protein (WRN) is a member of the recQ gene family, but unlike other members of the recQ family, it contains a unique 3'-->5' exonuclease activity. We have reported previously that human Ku heterodimer interacts physically with WRN and functionally stimulates WRN exonuclease activity. Because Ku and DNA-PKcs, the catalytic subunit of DNA-dependent protein kinase (DNA-PK), form a complex at DNA ends, we have now explored the possibility of functional modulation of WRN exonuclease activity by DNA-PK. We find that although DNA-PKcs alone does not affect the WRN exonuclease activity, the additional presence of Ku mediates a marked inhibition of it. The inhibition of WRN exonuclease by DNA-PKcs requires the kinase activity of DNA-PKcs. WRN is a target for DNA-PKcs phosphorylation, and this phosphorylation requires the presence of Ku. We also find that treatment of recombinant WRN with a Ser/Thr phosphatase enhances WRN exonuclease and helicase activities and that WRN catalytic activity can be inhibited by rephosphorylation of WRN with DNA-PK. Thus, the level of phosphorylation of WRN appears to regulate its catalytic activities. WRN forms a complex, both in vitro and in vivo, with DNA-PKC. WRN is phosphorylated in vivo after treatment of cells with DNA-damaging agents in a pathway that requires DNA-PKcs. Thus, WRN protein is a target for DNA-PK phosphorylation in vitro and in vivo, and this phosphorylation may be a way of regulating its different catalytic activities, possibly in the repair of DNA dsb.
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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/DNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Activated Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Exodeoxyribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PRKDC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RecQ Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/WRN protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18291-302
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11889123-Animals,
pubmed-meshheading:11889123-Base Sequence,
pubmed-meshheading:11889123-Catalysis,
pubmed-meshheading:11889123-Catalytic Domain,
pubmed-meshheading:11889123-DNA Damage,
pubmed-meshheading:11889123-DNA Helicases,
pubmed-meshheading:11889123-DNA Primers,
pubmed-meshheading:11889123-DNA-Activated Protein Kinase,
pubmed-meshheading:11889123-DNA-Binding Proteins,
pubmed-meshheading:11889123-Exodeoxyribonucleases,
pubmed-meshheading:11889123-HeLa Cells,
pubmed-meshheading:11889123-Humans,
pubmed-meshheading:11889123-Insects,
pubmed-meshheading:11889123-Nuclear Proteins,
pubmed-meshheading:11889123-Phosphorylation,
pubmed-meshheading:11889123-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11889123-RecQ Helicases,
pubmed-meshheading:11889123-Recombinant Proteins,
pubmed-meshheading:11889123-Werner Syndrome
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pubmed:year |
2002
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pubmed:articleTitle |
Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation.
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pubmed:affiliation |
Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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