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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-7-15
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pubmed:abstractText |
Inactivation of topoisomerase (topo) IIalpha arrests murine embryonic development. In topo IIalpha-depleted embryos, nuclei were partitioned to daughter cells without complete separation and formed an interconnecting droplet-like structure. The present study examined the fates of topo IIalpha-depleted cells with the droplet-like nuclear structure. When the embryos with abnormal nuclei were further incubated, apoptosis was induced along with the formation of fragmented and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling positive nuclei. ICRF-193 treatment of embryos activated caspases. Apoptosis induced by ICRF-193 was suppressed by z-VAD-fmk, a caspase inhibitor, and pifithrin-alpha, a p53 inhibitor. Moreover, when mitosis was blocked by nocodazole, ICRF-193-induced nuclear abnormalities and apoptosis were abolished. These data suggest that cycling through the M-phase is essential for ICRF-193-induced apoptosis. Nuclear abnormalities similar to those of topo IIalpha-depleted embryos were induced in HeLa cells in which topo IIalpha was knocked down by transfection with short interfering RNA (siRNA) against topo IIalpha, followed by induction of apoptosis. Our results suggest that topo IIalpha-depleted cells with the droplet-like nuclear structure induce apoptosis, which is dependent on caspase and p53 activity during the G1 phase in mammalian cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4,4'-(1,2-dimethyl-1,2-ethanediyl)bi...,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzothiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type II,
http://linkedlifedata.com/resource/pubmed/chemical/DNA topoisomerase II alpha,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Nocodazole,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Toluene,
http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase II Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/pifithrin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
307
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
301-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12859955-Animals,
pubmed-meshheading:12859955-Antigens, Neoplasm,
pubmed-meshheading:12859955-Antineoplastic Agents,
pubmed-meshheading:12859955-Apoptosis,
pubmed-meshheading:12859955-Benzothiazoles,
pubmed-meshheading:12859955-Caspases,
pubmed-meshheading:12859955-Cell Nucleus,
pubmed-meshheading:12859955-DNA Topoisomerases, Type II,
pubmed-meshheading:12859955-DNA-Binding Proteins,
pubmed-meshheading:12859955-Embryo, Mammalian,
pubmed-meshheading:12859955-Enzyme Activation,
pubmed-meshheading:12859955-Fluorescent Dyes,
pubmed-meshheading:12859955-HeLa Cells,
pubmed-meshheading:12859955-Humans,
pubmed-meshheading:12859955-In Situ Nick-End Labeling,
pubmed-meshheading:12859955-Mice,
pubmed-meshheading:12859955-Mice, Knockout,
pubmed-meshheading:12859955-Nocodazole,
pubmed-meshheading:12859955-Piperazines,
pubmed-meshheading:12859955-RNA, Small Interfering,
pubmed-meshheading:12859955-Thiazoles,
pubmed-meshheading:12859955-Toluene,
pubmed-meshheading:12859955-Topoisomerase II Inhibitors
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pubmed:year |
2003
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pubmed:articleTitle |
Induction of apoptosis by depletion of DNA topoisomerase IIalpha in mammalian cells.
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pubmed:affiliation |
Laboratory of Developmental Biochemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 3-1, 7-Chome, Hongo, Bunkyo-ku, Tokyo-shi, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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