Eukaryotic DNA topoisomerase I is active in transcribed chromatin domains to modulate transcription-generated DNA torsional tension. Camptothecin and other agents targeting DNA topoisomerase I are used in the treatment of human solid cancers with significant clinical efficacy. Major progress has been achieved in recent years in the understanding of enzyme structures and basic cellular functions of DNA topoisomerase I. Nevertheless, the precise enzyme functions and mechanisms during transcription-related processes remain unclear. The current understanding of the molecular action of camptothecin emphasizes the drug action against the enzyme and the production of irreversible breaks in the cellular DNA. However, the high drug potency is hardly fully explained by the DNA damage outcome only. In the recent past, several unexpected findings have been reported in relation to the role of eukaryotic topoisomerase I during transcription. In particular, the function of DNA topoisomerase I and the molecular effects of its inhibition on transcription-coupled processes constitute a very active research area. Here, we will briefly review relevant investigations on topoisomerase I involvement in different stages of transcription, discussing both enzyme functions and drug effects on molecular processes.

The effects of camptothecin on RNA polymerase II transcription: roles of DNA topoisomerase I.

CAPRANICO, GIOVANNI;FERRI, FRANCESCA;FOGLI, MARIA VITTORIA;RUSSO, ALESSANDRA;LOTITO, LUCA;BARANELLO, LAURA
2007

Abstract

Eukaryotic DNA topoisomerase I is active in transcribed chromatin domains to modulate transcription-generated DNA torsional tension. Camptothecin and other agents targeting DNA topoisomerase I are used in the treatment of human solid cancers with significant clinical efficacy. Major progress has been achieved in recent years in the understanding of enzyme structures and basic cellular functions of DNA topoisomerase I. Nevertheless, the precise enzyme functions and mechanisms during transcription-related processes remain unclear. The current understanding of the molecular action of camptothecin emphasizes the drug action against the enzyme and the production of irreversible breaks in the cellular DNA. However, the high drug potency is hardly fully explained by the DNA damage outcome only. In the recent past, several unexpected findings have been reported in relation to the role of eukaryotic topoisomerase I during transcription. In particular, the function of DNA topoisomerase I and the molecular effects of its inhibition on transcription-coupled processes constitute a very active research area. Here, we will briefly review relevant investigations on topoisomerase I involvement in different stages of transcription, discussing both enzyme functions and drug effects on molecular processes.
2007
Capranico G.; Ferri F.; Fogli M.V.; Russo A.; Lotito L.; Baranello L.
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/46347
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 44
  • ???jsp.display-item.citation.isi??? 43
social impact