DNA cleavage mechanism

Burger RM, Projan SJ, Horwitz SB, Peisach J (1986) The DNA cleavage mechanism of iron-bleomycin. J Biol Chem 261 15955-15959... 

Endonucleases. Endonucleases provide for DNA cleavage into small ( 200 base pairs) fragments, which is an essential step in apoptotic cascade (Wyllie 1980 Wyllie 1998). Endonucleases are stimulated by Ca2+ and their activation was detected in several cell types undergoing apoptosis (McConkey et al., 1988 Aw et al., 1990). The intimate mechanisms of endonucleases action remain not fully described at least in part they can be explained through the involvement of caspase-3 activated endonuclease (or caspase-activated DNAase - (Enari et al., 1998)). Nonetheless, the chromatin fragmentation was also observed in cell (and caspase)-free system, when isolated nuclei were treated with Ca2+ and ATP, suggesting the existence of caspase-independent DNA cleavage mechanism (Jones et al., 1989). 

A markedly different proposal for the DNA cleavage mechanism (from that reported by Leszczynski s) group was published by us in 2005 [36], To the best of our knowledge this was the first mechanism presented in the literature for single strand break formation to be based on the formation of stable valence anions of nucle-obases. Figure 21-29 displays the main idea of our suggestion for the C3 -0 bond scission in 3 -phosphate of cytidine. 

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