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This protective mechanism, active exclusively after e5.5 and lost during gastrulation, ensures the elimination of every mutated cell before its clonal expansion, and is therefore expected to greatly increase individuals' fitness.<\/jats:p><jats:p>We show that the insurgence of apoptosis relies on the epiblast-specific convergence of both increased DNA damage signalling and stronger pro-apoptotic balance. Although upstream Atm\/Atr global activity and specific \u03b3H2AX phosphorylation are similar in all cell types of the embryo, 53BP1 recruitment at DNA breaks is immediately amplified only in epiblast cells after ionizing radiation. This correlates with a rapid epiblast-specific activation of p53 and its transcriptional properties. Moreover, between e5.5 and e6.5, epiblast cells lower their apoptotic threshold by overexpressing pro-apoptotic Bak and Bim and repressing the anti-apoptotic Bcl-xL. Thus even after low dose irradiation, the cytoplasmic priming of epiblast cells allows p53 to rapidly induce apoptosis via a partially transcription-independent mechanism.<\/jats:p>","DOI":"10.1242\/dev.125708","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T03:38:24Z","timestamp":1442979504000},"source":"Crossref","is-referenced-by-count":13,"title":["Differential DNA damage signalling and apoptotic threshold correlate with mouse epiblast-specific hypersensitivity to radiation"],"prefix":"10.1242","author":[{"given":"Audrey","family":"Laurent","sequence":"first","affiliation":[{"name":"IFOM (FIRC Institute of Molecular Oncology), IFOM-IEO-Campus, Via Adamello 16, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Blasi","sequence":"additional","affiliation":[{"name":"IFOM (FIRC Institute of Molecular Oncology), IFOM-IEO-Campus, Via Adamello 16, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042608132556300_DEV125708C1","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1128\/MCB.21.5.1719-1729.2001","article-title":"Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage","volume":"21","author":"Anderson","year":"2001","journal-title":"Mol. 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