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In particular, the failure of AT cells to arrest transiently the DNA <jats:italic>de novo<\/jats:italic> replication machinery immediately after irradiation\u2014so\u2010called radioresistant DNA synthesis (RDS)\u2014is often taken as a molecular hallmark of the disease. Recently we reported that: (i) the radiation\u2010responsive S\u2010phase checkpoint operating in normal human cells is mediated by a signal transduction pathway involving Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent protein kinase II (CaMKII); and (ii) the RDS phenotype of AT cells is associated with failure to mobilize Ca<jats:sup>2+<\/jats:sup> from intracellular stores, which is required for activation of the CaMKII\u2010dependent S\u2010phase arrest. In the present study, we demonstrate that the RDS phenotype of AT dermal fibroblasts can be rectified in the absence of ectopic expression of functional ATM, the 350\u2010kDa protein kinase encoded by the gene mutated in AT. Correction of RDS was observed when AT fibroblasts were coincubated with normal fibroblasts under conditions in which the 2 different cell cultures shared the same medium but were completely separated physically. The RDS trait was also rectified when AT fibroblasts were briefly incubated with prostaglandin E<jats:sub>2<\/jats:sub> in the absence of normal feeder cells, signifying that this ubiquitous eicosanoid can serve as the diffusible \u201cRDS\u2010correction factor\u201d for AT cells in the aforementioned cocultivation studies. It would therefore appear that prostaglandin E<jats:sub>2<\/jats:sub> can assume the role of an extracellular signaling modulator of the S\u2010phase checkpoint in AT cells exposed to ionizing radiation, inducing DNA synthesis shutdown via an alternative, ATM\u2010independent signal transduction pathway. Environ. Mol. Mutagen. 38:191\u2013199, 2001 \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/em.1071","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:15:54Z","timestamp":1030310154000},"page":"191-199","source":"Crossref","is-referenced-by-count":2,"title":["Correction of radioresistant DNA synthesis in ataxia telangiectasia fibroblasts by prostaglandin E<sub>2<\/sub> treatment"],"prefix":"10.1002","volume":"38","author":[{"given":"Razmik","family":"Mirzayans","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm 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