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
More filters
Journal ArticleDOI
Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence
TL;DR: Higher-order unfolding of peri/centromeric satellite DNA is a consistent and early event in senescence of cultured normal human and mouse cells, progeria cells, and a senescent tumor.
Journal ArticleDOI
A Suv39h-dependent mechanism for silencing S-phase genes in differentiating but not in cycling cells.
Slimane Ait-Si-Ali,Valentina Guasconi,Lauriane Fritsch,Hakima Yahi,Redha Sekhri,Irina Naguibneva,Philippe Robin,Florence Cabon,Anna Polesskaya,Annick Harel-Bellan +9 more
TL;DR: Results indicate that the E2F target gene permanent silencing mechanism that is triggered upon terminal differentiation is distinct from the transient repression mechanism in cycling cells, and appropriately timed H3K9 methylation by Suv39h seems to be part of the control switch for exiting the cell cycle and entering differentiation.
Journal ArticleDOI
Granule exocytosis mediates immune surveillance of senescent cells
Adi Sagiv,Anat Biran,Monica Yon,Monica Yon,Janelle Simon,Janelle Simon,Scott W. Lowe,Scott W. Lowe,Valery Krizhanovsky,Valery Krizhanovsky +9 more
TL;DR: It is shown that granule exocytosis, but not death-receptor-mediated apoptosis, is required for NK-cell-mediated killing of senescent cells, and this results provide new insights into the immune surveillance of senescence and reveal how granuleExocytotic has a protective role against liver fibrosis.
Journal ArticleDOI
Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction
TL;DR: Present data point to a more important role of oxidative stress for the maximal healthspan (healthy aging) than for the maximum lifespan, with special emphasis on mitochondrial ROS formation and oxidative damage of mitochondrial DNA.
Journal ArticleDOI
Activated p53 suppresses the histone methyltransferase EZH2 gene
TL;DR: It is suggested that the p 53-dependent suppression of EZH2 expression is a novel pathway that contributes to p53-mediated G2/M arrest and may lead to novel approaches to control cancer progression.
References
More filters
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.