Linked Life Data

11889123

Source:http://linkedlifedata.com/resource/pubmed/id/11889123

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2002-5-20
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18291-302
pubmed:dateRevised
2009-11-19
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
pubmed:year
2002
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.
pubmed:affiliation
Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't