A novel antitumor compound, NC-190, induces topoisomerase II-dependent DNA cleavage and DNA fragmentation

1996 ◽  
Vol 38 (1) ◽  
pp. 29-34 ◽  
Author(s):  
T. Yamagishi ◽  
Shiro Nakaike ◽  
Tomotake Ikeda ◽  
Hisao Ikeya ◽  
Susumu Otomo
1995 ◽  
Vol 42 (2) ◽  
pp. 201-204 ◽  
Author(s):  
V T Solovyan ◽  
I O Andreyev

The treatment of agarose embedded plant nuclei by strong protein denaturants was demonstrated to result in discrete self-fragmentation of intact nuclear DNA. The set of resultant DNA cleavage products involves two main types of DNA fragments sized about 50-100 kb and 300-500 kb, being of the same type in various eukaryotic representatives. The pattern of ordered DNA fragmentation has been shown to be similar both in intact nuclei and in histone-depleted ones thus suggesting that the observed DNA fragments represent preexisting DNA structural domains, corresponding to the higher levels of chromatin folding. The topoisomerase II-specific poison teniposide (VM-26) has been shown to increase the ordered DNA cleavage while the conditions stimulating the topoisomerase II-mediated reverse reaction lead to the reassociation of the cleaved DNA domains. The data presented suggest that the nuclear DNA structural domains are involved in functioning of the topoisomerase II/DNA complex, the main property of which is its ability to mediate the cleavage/reassociation reactions.


1991 ◽  
Vol 19 (24) ◽  
pp. 7003-7003 ◽  
Author(s):  
Y. Pommier ◽  
G. Capranico ◽  
A. Orr ◽  
K.W. Kohn

FEBS Letters ◽  
1993 ◽  
Vol 334 (3) ◽  
pp. 369-372 ◽  
Author(s):  
Jean-François Riou ◽  
Michèle Gabillot ◽  
Guy Riou

1991 ◽  
Vol 95 (2) ◽  
pp. 659-662 ◽  
Author(s):  
Boe S. Sørensen ◽  
Hideki Fukata ◽  
Palle S. Jensen ◽  
Anni H. Andersen ◽  
Kent Christiansen ◽  
...  

1993 ◽  
Vol 71 (9-10) ◽  
pp. 488-500 ◽  
Author(s):  
Valerie M. Weaver ◽  
Boleslaw Lach ◽  
P. Roy Walker ◽  
Marianna Sikorska

Three chemically distinct serine, but not cysteine, protease inhibitors (phenylmethylsulphonyl fluoride, N-tosyl-L-phenylalanylchloromethyl ketone and 3,4-dichloroisocoumarin) prevented, in a dose-dependent manner, the characteristic apoptotic internucleosomal DNA cleavage (DNA ladder) typically observed in thymocytes in response to dexamethasone and teniposide VM-26. This effect was not the result of a direct inhibition of the Ca2+, Mg2+-dependent endonuclease, since oligonucleosomal DNA cleavage occurred in the presence of these inhibitors in isolated nuclei. The proteolytic step occurred at a very early stage of apoptosis, and preincubation of thymocytes with the inhibitors before dexamethasone or teniposide VM-26 were added irreversibly suppressed ladder formation. This implied that the cellular effector(s) of these compounds preexisted and were not resynthesized in response to the inducers of apoptosis. Serine protease inhibitors also suppressed apoptotic cell shrinkage and complete nuclear collapse, suggesting that these morphological changes were directly related to internucleosomal fragmentation of DNA. However, the serine protease inhibitors did not prevent high molecular weight DNA cleavage (> 50 kilobases) that preceded the ladder formation and thymocytes still died by apoptosis. This supported the view that internucleosomal DNA cleavage, considered to be the biochemical marker of apoptosis, might in fact be a late and dispensable step and that the newly described high molecular weight DNA cleavage might be a better indicator of apoptosis.Key words: serine protease, apoptosis, internucleosomal DNA fragmentation, high molecular weight DNA cleavage, protease inhibitors.


Biochemistry ◽  
1988 ◽  
Vol 27 (24) ◽  
pp. 8861-8869 ◽  
Author(s):  
Mary K. Danks ◽  
Carla A. Schmidt ◽  
Margaret C. Cirtain ◽  
D. Parker Suttle ◽  
William T. Beck

1995 ◽  
Vol 213 (1) ◽  
pp. 282-288 ◽  
Author(s):  
M. Govoni ◽  
S. Neri ◽  
T. Labella ◽  
J.E. Sylvester ◽  
F. Novello ◽  
...  

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