DNA FRAGMENTATION INTO 200-250-KILOBASE AND/OR 30-50-KILOBASE PAIR FRAGMENTS IN RAT-LIVER NUCLEI IS STIMULATED BY MG2+ ALONE AND CA2+/MG2+ BUT NOT BY CA2+ ALONE

Internucleosomal cleavage of DNA has often been regarded as the biochemical hallmark of apoptosis. We now demonstrate in isolated rat liver nuclei that DNA is initially cleaved into greater than or equal to 700, 200-250 kbp and 30-50 kbp fragments via a multi-step process, which is activated by Mg2+ and Mg2++Ca2+ but not by Ca2+ 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 Mg2+ -dependent process (which can be potentiated by Ca2+) and/or by a Ca2+/Mg2+ activated endonuclease(s).