Processing of topoisomerase I cleavable complexes into DNA damage by transcription.
AUTOR(ES)
Wu, J
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=147056Documentos Relacionados
- Transcription-Dependent Degradation of Topoisomerase I-DNA Covalent Complexes
- Inhibition of replicon initiation in human cells following stabilization of topoisomerase-DNA cleavable complexes.
- Stabilization of type I topoisomerase-DNA covalent complexes by actinomycin D.
- Plasmid linking number change induced by topoisomerase I-mediated DNA damage.
- Processing of nucleopeptides mimicking the topoisomerase I–DNA covalent complex by tyrosyl-DNA phosphodiesterase
