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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Senescence-Induced Vascular Remodeling Creates Therapeutic Vulnerabilities in Pancreas Cancer.
Marcus Ruscetti,John P. Morris,Riccardo Mezzadra,James A. Russell,Josef Leibold,Paul B. Romesser,Janelle Simon,Amanda Kulick,Yu-Jui Ho,Myles Fennell,Jinyang Li,Robert J. Norgard,John E. Wilkinson,Direna Alonso-Curbelo,Ramya Sridharan,Ramya Sridharan,Daniel A. Heller,Daniel A. Heller,Elisa de Stanchina,Ben Z. Stanger,Charles J. Sherr,Scott W. Lowe,Scott W. Lowe +22 more
TL;DR: In PDAC models, therapy-induced senescence can establish emergent susceptibilities to otherwise ineffective chemo- and immunotherapies through SASP-dependent effects on the tumor vasculature and immune system.
Journal ArticleDOI
Long noncoding RNA PANDA and scaffold-attachment-factor SAFA control senescence entry and exit
Pavan Kumar Puvvula,Rohini Devi Desetty,Pascal Pineau,Agnès Marchio,Anne M. Moon,Anne Dejean,Oliver Bischof +6 more
TL;DR: It is demonstrated that PANDA confines cells to their existing proliferative state and that modulating its level of expression can cause entry or exit from senescence.
Journal ArticleDOI
MacroH2A1 and ATM Play Opposing Roles in Paracrine Senescence and the Senescence-Associated Secretory Phenotype.
Hongshan Chen,Penelope D. Ruiz,Wendy M. McKimpson,Leonid Novikov,Richard N. Kitsis,Matthew J. Gamble +5 more
TL;DR: It is demonstrated that the tumor suppressive histone variant macroH2A1 is a critical component of the positive feedback loop that maintains SASP gene expression and triggers the induction of paracrine senescence.
Journal ArticleDOI
A comparative analysis of the cell biology of senescence and aging
TL;DR: Comparison of age-related changes and their underlying mechanisms in in vitro senescent cells and aged postmitotic cells would reveal the relevance of replicative senescence to the physiological processes occurring in postmitosis cells as individuals age.
Journal ArticleDOI
Global heterochromatin loss: a unifying theory of aging?
Amy Tsurumi,Willis X. Li +1 more
TL;DR: The objective of this Point-of-View is to highlight recent progress on the “loss of heterochromatin” model of aging and to propose that epigenetic changes contributing to global heterochrome loss may underlie the various cellular processes associated with 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.
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.
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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.