Targeted disruption of the mouse topoisomerase I gene by camptothecin selection
نویسندگان
چکیده
منابع مشابه
Targeted disruption of the mouse topoisomerase I gene by camptothecin selection.
Topoisomerase I has ubiquitous roles in important cellular functions such as replication, transcription, and recombination. In order to further characterize this enzyme in vivo, we have used gene targeting to inactivate the mouse Top-1 gene. A selection protocol using the topoisomerase I inhibitor camptothecin facilitated isolation of embryonic stem cell clones containing an inactivated allele;...
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DNA topoisomerase I (Top1) is a ubiquitous nuclear enzyme that plays essential roles in various cellular processes, such as transcription or replication. Agents that target Top1, involving camptothecin and its derivatives, are among the most effective anticancer drugs used in the clinic. Previous work has suggested that the level of Top1 expression correlates with the cytotoxicity of camptothec...
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Proteasomal degradation of topoisomerase I (topoI) is one of the most remarkable cellular phenomena observed in response to camptothecin (CPT). Importantly, the rate of topoI degradation is linked to CPT resistance. Formation of the topoI-DNA-CPT cleavable complex inhibits DNA re-ligation resulting in DNA-double strand break (DSB). The degradation of topoI marks the first step in the ubiquitin ...
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ژورنال
عنوان ژورنال: Molecular and Cellular Biology
سال: 1996
ISSN: 0270-7306,1098-5549
DOI: 10.1128/mcb.16.12.6804