Linked Life Data

17136094

Source:http://linkedlifedata.com/resource/pubmed/id/17136094

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7119
pubmed:dateCreated
2006-11-30
pubmed:abstractText
Early tumorigenesis is associated with the engagement of the DNA-damage checkpoint response (DDR). Cell proliferation and transformation induced by oncogene activation are restrained by cellular senescence. It is unclear whether DDR activation and oncogene-induced senescence (OIS) are causally linked. Here we show that senescence, triggered by the expression of an activated oncogene (H-RasV12) in normal human cells, is a consequence of the activation of a robust DDR. Experimental inactivation of DDR abrogates OIS and promotes cell transformation. DDR and OIS are established after a hyper-replicative phase occurring immediately after oncogene expression. Senescent cells arrest with partly replicated DNA and with DNA replication origins having fired multiple times. In vivo DNA labelling and molecular DNA combing reveal that oncogene activation leads to augmented numbers of active replicons and to alterations in DNA replication fork progression. We also show that oncogene expression does not trigger a DDR in the absence of DNA replication. Last, we show that oncogene activation is associated with DDR activation in a mouse model in vivo. We propose that OIS results from the enforcement of a DDR triggered by oncogene-induced DNA hyper-replication.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
444
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
638-42
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication.
pubmed:affiliation
IFOM Foundation-FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't