Abstract
In several cell types, apoptosis is associated with intracellular acidification and activation of a pH-dependent endonuclease. We have examined the effect of acidic pH on the DNA of permeabilized human fibroblasts, and observed cleavage of DNA into high-molecular-mass fragments. This pH-dependent DNA breakage was modulated by temperature, the presence of histones and diethyl pyrocarbonate. Superoxide dismutase and chelators with high affinity for Cu prevented DNA fragmentation, whereas catalase, DMSO and Desferal (desferrioxamine mesylate) offered no protection. Fragmentation of DNA into high-molecular-mass fragments, which is occasionally observed as an early phase of apoptosis, is thought to result from the activation of endonuclease(s). Our results suggest that such fragmentation also occurs through induction of copper-mediated site-specific DNA damage that is enhanced by intracellular acidification.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
