Apoptotic topoisomerase I-DNA complexes induced by oxygen radicals and mitochondrial dysfunction.
Topoisomerase I (Top1) is expressed throughout the cell cycle. Top1 forms reversible and transient DNA cleavage complexes as it relaxes DNA supercoiling generated by transcription and replication. Recent findings indicate that mechanistically different inducers of apoptosis, arsenic trioxide, staurosporine and etoposide, which are inactive on purified Top1, induce Top1 cleavage complexes. These apoptotic Top1 cleavage complexes result from oxidative DNA lesions generated by reactive oxygen species during apoptosis. Their functional role could be to directly fragment chromatin and to further activate (amplify) apoptotic pathways.
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA.
Olivier
O
Sordet
Qasim A
QA
Khan
Yves
Y
Pommier
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D053938:DNA Fragmentation / Q000502:physiology; D004261:DNA Replication / Q000502:physiology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D046911:Macromolecular Substances; D017382:Reactive Oxygen Species; D004247:DNA; D004264:DNA Topoisomerases, Type I