Nuclear DNA fragmentation

Endonuclease-catalyzed hydrolysis of DNA at the internucleosomal linker regions into multimers of 180 base pairs which are visualized by electrophoresis as a ladder of nuclear DNA fragments. Access of the endonuclease to DNA is facilitated by depletion of polyamines, and the activity of the enzyme is mcrea.sed by and decreased by ADP-tibosylation. Thus, agents that increase intracellular Ca " or inhibit l>oly(ADP-ribose) polymerase can induce apoptosi.s. ... 

Gavrieli, Y., Sherman, Y., and Ben-Sasson, S. A. (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol. 119,493-501. 

Hara A., Yoshimi N., Mori H., et al. (1995) Hypothermic prevention of nuclear DNA fragmentation in gerbil hippocampus following transient forebrain ischemia. Neurol. Res. 17,461 164. 

Tsukube et al. (1994) investigated the relationship between cytosolic and nuclear calcium content in the ischemic myocardium. Their results indicated that, during ischemia, both cytosolic and nuclear calcium are augmented, with that of nuclear calcium being associated with increased nuclear DNA fragmentation. Treatment with Mg and a combination of Mg-K reduced the nuclear calcium accumulation and decreased the nuclear DNA fragmentation. 

The central nervous system of the ascidian tadpole larvae consist of 370 cells with PCNA proteins in the nuclei. An antisense oligonucleotide can inhibit the PCNA mRNA. Inhibition of PCNA resulted in deformed head development with cessation of DNA synthesis and nuclear DNA fragmentation resembling programmed cell death [1094]. The drosophila or mosquito dacapo is a Cip/Kip family cell cycle inhibitoiy protein of 261aa residues (cycline-dependent kinase inhibitory protein kinase inhibitory protein). The serine-threo/any aa/glutamate/aspartic acid... 

McGill, M.R., et al.. The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J Clin Invest, 2012. 122(4) p. 1574-83. 

TNF-a can mediate death of sensitive cells via apoptosis or necrosis (necrotic death is characterized by clumping of the nuclear chromatin, cellular swelling, disintegration of intracellular organelles and cell lysis apoptotic death is characterized by cellular shrinking, formation of dense apoptotic masses and DNA fragmentation). 

Berezney R, Buchholtz LA (1981) Dynamic association of repheating DNA fragments with the nuclear matrix of regenerating hver. Exp Cell Res 132(1) 1-13 Berezney R, Coffey DS (1974) Identification of a nuclear protein matrix. Biochem Biophys Res Commun 60(4) 1410-1417... 

Approaches to cloning DNA Genomic DNA Restriction endonucleases fragment DNA Total nuclear DNA cloned Genes contain introns cDNA Reverse transcription of mRNAs from cell Genes expressed cloned Genes have no introns... 

Apoptosis Nuclear condensation and lobulation, caspase activation, phosphatidyl serine externalization, annexin, immuno-cytochemistry, DNA fragmentation and labeled-dUTP incorporation by terminal deoxynucleotidyl transferase... 

The biochemical hallmark of apopfosis is fhe fragmentation of the genomic DNA, an irreversible event that commits the cells to die. This fragmentation in many cell types has been shown to result from the activation of an endogenous Ca +- and Mg +-dependent nuclear endonuclease (W18). This enzyme selectively cleaves DNA at sites located between nucleosomal units (linker DNA), generating mono- and oligonucleosomal DNA fragments. 

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