Heterochromatin and its relationship to cell senescence and cancer therapy.
Our goal is to understand the impact of chromatin structure on cell proliferation, cell and tissue aging, cancer and cancer therapies. Senescence associated heterochromatin foci (SAHF) are specialized domains of facultative heterochromatin that form in senescent human cells. Although SAHF are highly compacted domains of heterochromatin, they 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, we have obtained evidence for a novel function for a 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. Defects in this "chromatin repair" response in transformed cells may contribute to preferential killing of cancer cells by epigenetic cancer therapies, currently in clinical development.
Zhang
Rugang
R
Department of Basic Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Adams
Peter D
PD
D000818:Animals; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D006570:Heterochromatin / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D000090266:Chromobox Protein Homolog 5