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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The SWI/SNF chromatin remodelling complex: Its role in maintaining genome stability and preventing tumourigenesis
TL;DR: Some of the transcription-independent functions of the SWI/SNF chromatin remodelling complex are reviewed and discussed in light of their potential relevance to tumourigenesis.
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Structure-function analysis of the retinoblastoma tumor suppressor protein - is the whole a sum of its parts?
TL;DR: This review will focus on literature that investigates pRB by isolating functions based on binding sites within the pocket domain and the prospects for using this approach to further explore the unknown functions of pRB.
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Aging epigenetics: causes and consequences.
TL;DR: The process depends on genetic and environmental factors and, when it takes place in adult stem cells, it could play an important role in aging, although the underlying molecular mechanisms are still largely unknown.
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Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence
Jesse M. Platt,Paul Ryvkin,Jennifer J. Wanat,Greg Donahue,M. Dan Ricketts,Steven P. Barrett,Hannah J. Waters,Shufei Song,Alejandro Chavez,Khaled Omar Abdallah,Stephen R. Master,Li-San Wang,F. Brad Johnson +12 more
TL;DR: Rap1 relocalization is a novel mechanism connecting DNA damage responses at telomeres to global changes in chromatin and gene expression while driving the pace of senescence.
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MicroRNA-152 and -181a participate in human dermal fibroblasts senescence acting on cell adhesion and remodeling of the extra-cellular matrix
Mara Mancini,Gaelle Saintigny,Christian Mahé,Margherita Annicchiarico-Petruzzelli,Gerry Melino,Eleonora Candi +5 more
TL;DR: Findings indicate that changes in miRNAs expression, by modulating the levels of adhesion proteins and extra-cellular matrix components, such as integrin α and collagen XVI, could contribute to the compositional remodelling of the dermis and epidermis occurring during skin aging.
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.