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00925njm 22002777a 4500 dc Toledo, Luis I author Murga, Matilde author Gutierrez-Martinez, Paula author Soria, Rebeca author Fernandez-Capetillo, Oscar author 2008-02-01 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. Genes Dev . 2008 ;22(3):297-302. 0890-9369 http://hdl.handle.net/20.500.12105/17686 18245444 10.1101/gad.452308 Genes & development ATR signaling can drive cells into senescence in the absence of DNA breaks.