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Heterochromatin and its Relationship to Cell Senescence and Cancer Therapy
Rugang Zhang and Peter D. Adams
volume 6 | issue 7
1 April 2007Pages: 784 - 789
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Our goal is to understand the impact of chromatin structure on cell proliferation, cell and tissue aging, cancer and cancer therapies. To this end, we have investigated the formation of specialized domains of facultative heterochromatin, called Senescence Associated Heterochromatin Foci (SAHF), in senescent human cells. A complex of histone chaperones, HIRA and ASF1a, drives formation of SAHF. Remarkably, although SAHF are highly compacted domains of heterochromatin, these domains of facultative heterochromatin largely exclude other domains of chromatin at telomeres and pericentromeres, which are themselves thought to be constitutively heterochromatic. The relationship between SAHF formation and these other domains of heterochromatin is discussed. Also, in the course of our studies, we have obtained evidence that points to a novel function for the widely-studied but poorly-understood family of heterochromatin proteins, HP1 proteins. We propose that HP1 proteins are essential components of a dynamic nuclear response that senses and rectifies defects in epigenetic information, encoded in chromatin through histone modifications and DNA methylation. We further propose that defects in this essential "chromatin repair" response in transformed human cells contributes to the preferential killing of cancer cells by the epigenetic cancer therapies that are currently in clinical development.
Authors
Rugang Zhang
Fox Chase Cancer Center, Philadelphia, PA
Peter D. Adams
Fox Chase Cancer Center, Philadelphia, PA
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.