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Topoisomerase I Not Simply Adjusting Genome Topology

Topoisomerase I Not Simply Adjusting Genome Topology

Topoisomerases are well known to be essential for all aspects of DNA function, from replication to repair and particularly in transcription. For this reason, they have for many years been excellent DNA damaging agents that display selectively for tumor cells. A relatively recent finding has come to light that involves topoisomerase I and induction of cellular senescence. Cellular senescence is a form of tumor suppression that puts cells in a more or less permanent proliferative arrest. It is induced by truncated telomeres, DNA damage, or oncogene activation. Senescence is also associated with SAHF (Senescence Associated Heterochromatic Foci) characterized by localized regions of genetic shutdown (Nature Cell Biology 13: 292, 2011). Humbert et al (Cancer Res.69:4101, 2009) report that topo I knockdowns are associated with bypass of senescence in normal fibroblasts. In other words, topo I may be involved in regulating this process. Specifically, reducing topo I levels appear to increase replicative potential of normal cells. On the other hand, high ectopic expression of topo I favors growth arrest.

Article Source: Cancer Research Website

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