Processing of topoisomerase I cleavable complexes into DNA damage by transcription

Jiaxi Wu, Leroy-Fong Liu

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Topoisomerase I (TOP1)-mediated DNA damage induced by camptothecin (CPT) in the presence of active transcription has been studied using purified calf thymus TOP1 and T7 RNA polymerase. CPT-stabilized TOP1 cleavable complexes located on the template strand within the transcribed region were found to be into irreversible strand breaks by the RNA polymerase. By contrast, CPT-stabilized TOP1 cleavable complexes located on the non-template strand within the transcribed region was unaffected by the elongating RNA polymerase. Previous studies have demonstrated that the elongating T7 RNA polymerase is arrested by TOP1 cleavable complexes located on the template but not the non-template strand. Together, these results suggest a model in which collision between the TOP1-cleavable complexes located on the template strand and the elongating RNA polymerase results in transcription arrest and conversion of TOP1 cleavable complexes into 'irreversible' strand breaks. The implication of the transcription collision model in DNA damage and repair, as well as cell killing, is discussed.

Original languageEnglish
Pages (from-to)4181-4186
Number of pages6
JournalNucleic Acids Research
Volume25
Issue number21
DOIs
Publication statusPublished - Nov 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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