Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence.
Masashi Narita,Sabrina Nuñez,Sabrina Nuñez,Edith Heard,Masako Narita,Athena W. Lin,Stephen Hearn,David L. Spector,Gregory J. Hannon,Scott W. Lowe +9 more
TLDR
A distinct heterochromatic structure that accumulates in senescent human fibroblasts is described, which is designated senescence-associated heterochROMatic foci (SAHF) and is associated with the stable repression of E2F target genes.About:
This article is published in Cell.The article was published on 2003-06-13 and is currently open access. It has received 2055 citations till now. The article focuses on the topics: Senescence-associated heterochromatin focus & E2F.read more
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Defective DNA single-strand break repair is responsible for senescence and neoplastic escape of epithelial cells.
Joe Nassour,Sébastien Martien,Nathalie Martin,Emeric Deruy,Elisa Tomellini,Nicolas Malaquin,Fatima Bouali,Laure Sabatier,Nicolas Wernert,Sébastien Pinte,Sébastien Pinte,Eric Gilson,Albin Pourtier,Olivier Pluquet,Corinne Abbadie +14 more
TL;DR: It is shown that unlike fibroblasts, senescent epithelial cells do not activate an ATM-or ATR-dependent DNA damage response (DDR), but accumulate oxidative-stress-induced DNA single-strand breaks (SSBs) which could fuel the very first steps of carcinogenesis.
Journal ArticleDOI
Epigenetic Regulation of Cellular Senescence and Aging.
TL;DR: The role of epigenetic regulation in aging is discussed and future research directions that will help elucidate the mechanistic details of it are indicated.
Journal ArticleDOI
Heterochromatin and its relationship to cell senescence and cancer therapy.
Rugang Zhang,Peter D. Adams +1 more
TL;DR: It is proposed 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, that contributes to the preferential killing of cancer cells by the epigenetic cancer therapies that are currently in clinical development.
Journal ArticleDOI
Cell senescence: a challenge in cartilage engineering and regeneration.
Jingting Li,Ming Pei +1 more
TL;DR: Some potential factors resulting in cell senescence during cartilage tissue engineering, including ex vivo expansion, donor age, and degenerative diseases, and the challenge in the identification of senescent cells are summarized.
Journal ArticleDOI
Establishment of Patient-Derived Tumor Xenograft Models of Epithelial Ovarian Cancer for Preclinical Evaluation of Novel Therapeutics
Joyce F. Liu,Sangeetha Palakurthi,Qing Zeng,Shan Zhou,Elena Ivanova,Wei Huang,Ioannis K. Zervantonakis,Laura M. Selfors,Yiping Shen,Colin C. Pritchard,Mei Zheng,Vilmos Adleff,Eniko Papp,Huiying Piao,Marian Novak,Susan Fotheringham,Gerburg M. Wulf,Jessie M. English,Paul Kirschmeier,Victor E. Velculescu,Cloud P. Paweletz,Gordon B. Mills,David M. Livingston,Joan S. Brugge,Ursula A. Matulonis,Ronny Drapkin +25 more
TL;DR: A collection of 14 clinically annotated and molecularly characterized luciferized ovarian PDX models in which orthotopic tumor burden in the intraperitoneal space can be followed by standard and reproducible methods is described.
References
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A biomarker that identifies senescent human cells in culture and in aging skin in vivo
Goberdhan P. Dimri,X Lee,G Basile,Meileen Acosta,G Scott,C Roskelley,E E Medrano,Maarten H.K. Linskens,Ivica Rubelj,Olivia M. Pereira-Smith +9 more
TL;DR: It is shown that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture, which provides in situ evidence that senescent cells may exist and accumulate with age in vivo.
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The limited in vitro lifetime of human diploid cell strains
TL;DR: The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established.
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Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
TL;DR: It is shown that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest, and that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an onCogenic stimulus.
Journal ArticleDOI
Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.
TL;DR: It is shown that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins—a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure.
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Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.
Andrew J. Bannister,Philip Zegerman,Janet F. Partridge,Eric A. Miska,Jean O. Thomas,Robin C. Allshire,Tony Kouzarides +6 more
TL;DR: A stepwise model for the formation of a transcriptionally silent heterochromatin is provided: SUV39H1 places a ‘methyl marker’ on histone H3, which is then recognized by HP1 through its chromo domain, which may also explain the stable inheritance of theheterochromatic state.