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Titolo:
THE ANTICANCER DRUG CAMPTOTHECIN INHIBITS ELONGATION BUT STIMULATES INITIATION OF RNA-POLYMERASE-II TRANSCRIPTION
Autore:
LJUNGMAN M; HANAWALT PC;
Indirizzi:
UNIV MICHIGAN,MED CTR,DEPT RADIAT ONCOL,DIV CANC BIOL,1331 E ANN ST ANN ARBOR MI 48109 STANFORD UNIV,DEPT BIOL SCI STANFORD CA 94305
Titolo Testata:
Carcinogenesis
fascicolo: 1, volume: 17, anno: 1996,
pagine: 31 - 35
SICI:
0143-3334(1996)17:1<31:TADCIE>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA TOPOISOMERASE-I; DHFR GENE; CELLS; TOPOLOGY; STRAND; IDENTIFICATION; INVOLVEMENT; TEMPLATE; PROMOTER; ARREST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
M. Ljungman e P.C. Hanawalt, "THE ANTICANCER DRUG CAMPTOTHECIN INHIBITS ELONGATION BUT STIMULATES INITIATION OF RNA-POLYMERASE-II TRANSCRIPTION", Carcinogenesis, 17(1), 1996, pp. 31-35

Abstract

Camptothecin is a widely used anti-tumor drug that specifically inhibits DNA topoisomerase I. It is believed that topoisomerase I participates in the process of transcription by relaxing torsional stress induced in the duplex DNA by the elongating RNA polymerase. We have assessed the effects of camptothecin on RNA polymerase II transcription from the dihydrofolate reductase (DHFR) gene in Chinese hamster ovary (CHO)cells. Using in vivo [H-3]uridine pulse labeling and in vitro nuclearrun-on techniques to estimate relative rates of transcription, it wasfound that camptothecin stimulated RNA synthesis from promoter-proximal sequences of the DHFR gene, while transcription from promoter-distal sequences was reduced. Furthermore, camptothecin caused a significant accumulation of RNA polymerases in the 5'-end of the DHFR gene, The effect of camptothecin on transcription was reversible, resulting in awave of RNA synthesis recovery in a 5' to 3' direction through the DHFR gene following a chase with camptothecin-free medium. We conclude that camptothecin stimulates initiation but inhibits elongation of the RNA polymerase II transcribed DHFR gene.

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Documento generato il 30/11/20 alle ore 07:00:52