Linked Life Data

12598907

Source:http://linkedlifedata.com/resource/pubmed/id/12598907

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-3-20
pubmed:abstractText
Cell cycle checkpoints are signal transduction pathways activated after DNA damage to protect genomic integrity. Dynamic spatiotemporal coordination is a vital, but poorly understood aspect, of these checkpoints. Here, we provide evidence for a strikingly different behaviour of Chk2 versus Nbs1, key mediators of the ataxia-telangiecatesia-mutated (ATM)-controlled checkpoint pathways induced by DNA double-strand breaks (DSBs). In live human cells with DSBs restricted to small sub-nuclear areas, Nbs1 was rapidly recruited to the damaged regions and underwent a dynamic exchange in the close vicinity of the DSB sites. In contrast, Chk2 continued to rapidly move throughout the entire nucleus, irrespective of DNA damage and including the DSB-free areas. Although phosphorylation of Chk2 by ATM occurred exclusively at the DSB sites, forced immobilization of Chk2 to spatially restricted, DSB-containing nuclear areas impaired its stimulating effect on p53-dependent transcription. These results unravel a dynamic nature of Nbs1 interaction with DSB lesions and identify Chk2 as a candidate transmitter of the checkpoint signal, allowing for a coordinated pan-nuclear response to focal DNA damage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1465-7392
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
255-60
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage.
pubmed:affiliation
Danish Cancer Society, Institute of Cancer Biology, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. lucas@biobase.dk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't