Nucleic Acids Research, Vol 25, Issue 21 4181-4186, Copyright © 1997 by Oxford University Press
J Wu and LF Liu
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 converted into irreversible strand breaks by the elongating 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 [Bendixen et al .,
(1990) Biochemistry , 29, 5613-5619]. 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.
ARTICLES
Processing of topoisomerase I cleavable complexes into DNA damage by transcription
Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
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