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
Citations
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Senescent cells harbour features of the cancer epigenome
Hazel A Cruickshanks,Hazel A Cruickshanks,Tony McBryan,David M. Nelson,Nathan D. VanderKraats,Parisha P. Shah,John van Tuyn,Taranjit Singh Rai,Taranjit Singh Rai,Claire Brock,Greg Donahue,Donncha S. Dunican,Mark E. Drotar,Richard R. Meehan,John R. Edwards,Shelley L. Berger,Peter D. Adams +16 more
TL;DR: It is shown by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation, and this ‘reprogrammed’ methylation landscape is largely retained when cells bypass senescence.
Journal ArticleDOI
The requirement for cyclin D function in tumor maintenance.
Yoon Jong Choi,Xiaoyu Li,Per Hydbring,Takaomi Sanda,Takaomi Sanda,Joanna Stefano,Amanda L. Christie,Sabina Signoretti,Sabina Signoretti,A. Thomas Look,A. Thomas Look,Andrew L. Kung,Harald von Boehmer,Piotr Sicinski +13 more
TL;DR: Mice strains are engineered that allow acute and global ablation of individual D-cyclins in a living animal and inhibition of cyclin D-associated kinase activity represents a highly-selective anticancer strategy that specifically targets cancer cells without significantly affecting normal tissues.
Journal ArticleDOI
Mitochondrial effectors of cellular senescence: beyond the free radical theory of aging.
TL;DR: The role of mitochondrial reactive oxygen species (ROS), mitochondrial dynamics (fission and fusion), the electron transport chain (ETC), bioenergetic balance, redox state, metabolic signature, and calcium homeostasis in controlling cellular growth arrest are discussed.
Journal ArticleDOI
Control of the reversibility of cellular quiescence by the transcriptional repressor HES1.
TL;DR: It is concluded that HES1 safeguards against irreversible cell cycle exit both during normal cellular quiescence and pathologically in the setting of tumorigenesis.
Journal ArticleDOI
Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease
TL;DR: This review explores mechanisms that influence age-related large elastic artery stiffening and endothelial dysfunction at the tissue level via inflammation and oxidative stress and at the cellular level via Klotho and energy-sensing pathways (AMPK,AMP-activated protein kinase, SIRT, and mTOR).
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.
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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.