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We now demonstrate in isolated rat liver nuclei that DNA is initially cleaved into \u2a7e700, 200\u2013250 kbp and 30\u201350 kbp fragments via a multi\u2010step process, which is activated by Mg<jats:sup>+<\/jats:sup> and Mg<jats:sup>2+<\/jats:sup>+Ca<jats:sup>2+<\/jats:sup> but not by Ca<jats:sup>2+<\/jats:sup> alone. The subsequent internucleosomal cleavage requires both cations. These findings demonstrate that a key event in the apoptotic process is the fragmentation of DNA into large kbp fragments by either a Mg<jats:sup>2+<\/jats:sup> \u2010dependent process (which can be potentiated by Ca<jats:sup>2+<\/jats:sup>) and\/or by a Ca<jats:sup>2+<\/jats:sup>\/Mg<jats:sup>2+<\/jats:sup> activated endonuclease(s).<\/jats:p>","DOI":"10.1016\/0014-5793(94)80001-4","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T07:40:55Z","timestamp":1027582855000},"page":"385-391","source":"Crossref","is-referenced-by-count":27,"title":["DNA fragmentation into 200\u2013250 and\/or 30\u201350 kilobase pair fragments in rat liver nuclei is stimulated by Mg<sup>2+<\/sup> alone and Ca<sup>2+<\/sup>\/Mg<sup>2+<\/sup> but not by Ca<sup>2+<\/sup> alone"],"prefix":"10.1002","volume":"349","author":[{"given":"Kelvin","family":"Cain","sequence":"first","affiliation":[]},{"given":"Salmaan H.","family":"Inayat-Hussain","sequence":"additional","affiliation":[]},{"given":"James T.","family":"Wolfe","sequence":"additional","affiliation":[]},{"given":"Gerald M.","family":"Cohen","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2001,10,18]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00048057"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/284555a0"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00048058"},{"key":"e_1_2_1_5_1","first-page":"133","volume":"14","author":"Schwartzman R.A.","year":"1993","journal-title":"Endocr. 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