DNA topoisomerase I: Customs officer at the border between DNA and RNA worlds?

Jamal Tazi, Ferdinand Rossi, Emmanuel Labourier, Imed Edine Gallouzi, Claude Brunel, Etienne Antoine

Research output: Contribution to journalReview article

34 Citations (Scopus)

Abstract

DNA topoisomerase I is required for the normal development of multicellular organisms, probably because it plays a role in controlling gene activity, in addition to its function in relieving tortional stress during DNA replication and transcription. The discovery of DNA topoisomerase I as a specific kinase that phosphorylates serine-arginine rich (SR) splicing factors may provide new insights into their precise function in regulating gene expression. It is clear that the splicing factors phosphorylated by DNA topoisomerase I can modulate gene expression by changing the splicing pattern of structural genes. Studies of the splicing mechanism suggest that the phosphorylation of serine residues of SR proteins contribute to their activity. As this phosphorylation can be accomplished by several kinases, it remains to be determined whether phosphorylation by DNA topoisomerase I protein kinase is the limiting step in regulating this process. The availability of specific inhibitors of DNA topoisomerase I, structurally related to the alkaloid camptothecin, have made it possible to address this question experimentally. These inhibitors, which hold great promise as antineoplastic drugs, lead to specific inhibition of SR protein phosphorylation in cultured cells. This observation will hopefully lead to improved understanding of the mechanism by which these drugs act at cellular level.

Original languageEnglish
Pages (from-to)786-800
Number of pages15
JournalJournal of Molecular Medicine
Volume75
Issue number11-12
DOIs
Publication statusPublished - 1 Jan 1997

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Keywords

  • Alternative splicing
  • DNA topoisomerase I
  • Nucleus
  • Protein kinase
  • Protein phosphorylation
  • Small nuclear Ribonucleoprotein
  • Splicing factors
  • mRNA precursor

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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