Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17686
Título
ATR signaling can drive cells into senescence in the absence of DNA breaks.
Autor(es)
Fecha de publicación
2008-02-01
Cita
Genes Dev . 2008 ;22(3):297-302.
Idioma
Inglés
Tipo de documento
journal article
Resumen
The ATR kinase is a key transducer of "replicative stress," the type of genomic damage that has been postulated to be induced by oncogenes. Here we describe a cellular system in which we can unleash ATR activity at will, in the absence of any actual damage or additional signaling pathways triggered by DNA breaks. We demonstrate that activating ATR is sufficient to promote cell cycle arrest and, if persistent, triggers p53-dependent but Ink4a/ARF-independent senescence. Moreover, we show that an ectopic activation of ATR leads to a G1/S arrest in ATM-/- cells, providing the first evidence of functional complementation of ATM deficiency by ATR. Our system provides a novel platform for the study of the specific functions of ATR signaling and adds evidence for the tumor-suppressive potential of the DNA damage response.
MESH
DNA Breaks | Animals | Ataxia Telangiectasia Mutated Proteins | Cell Cycle | Cell Cycle Proteins | Cell Line, Transformed | Cell Line, Tumor | Cellular Senescence | Cyclin-Dependent Kinase Inhibitor p16 | DNA-Binding Proteins | Enzyme Activation | Humans | Mice | Protein Serine-Threonine Kinases | Signal Transduction | Tumor Suppressor Protein p53 | Tumor Suppressor Proteins
Versión en línea
DOI
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- atrsihnaling_2008.pdf
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