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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Vemurafenib Induces Senescence Features in Melanoma Cells
Sebastian Haferkamp,Andreas Borst,Christian Adam,Therese M. Becker,Stephanie Motschenbacher,Simone Windhövel,Anita Hufnagel,Roland Houben,Svenja Meierjohann +8 more
TL;DR: It is demonstrated, using a large panel of melanoma cell lines, that Vemurafenib induces features of stress-induced senescence in addition to apoptosis, which may provide a possible explanation for the lack of complete and durable pro-apoptotic effect of VemuFenib in patients.
Journal ArticleDOI
Maximal killing of lymphoma cells by DNA damage-inducing therapy requires not only the p53 targets Puma and Noxa, but also Bim
Lina Happo,Lina Happo,Mark S. Cragg,Belinda Phipson,Belinda Phipson,Jon M. Haga,Jon M. Haga,Elisa S. Jansen,Marco J Herold,Grant Dewson,Grant Dewson,Ewa M. Michalak,Ewa M. Michalak,Cassandra J. Vandenberg,Cassandra J. Vandenberg,Gordon K. Smyth,Gordon K. Smyth,Andreas Strasser,Andreas Strasser,Suzanne Cory,Suzanne Cory,Clare L. Scott,Clare L. Scott +22 more
TL;DR: The combinatorial action of Puma, Noxa, and Bim is critical for optimal apoptotic responses of lymphoma cells to 2 commonly used DNA-damaging chemotherapeutic agents, identifying Bim as an additional biomarker for treatment outcome in the clinic.
Journal ArticleDOI
CENP-A reduction induces a p53-dependent cellular senescence response to protect cells from executing defective mitoses.
TL;DR: It is proposed that p53-dependent senescence that arises from CENP-A reduction acts as a “self-defense mechanism” to prevent centromere-defective cells from undergoing mitotic proliferation that potentially leads to massive generation of aneuploid cells.
Journal ArticleDOI
Gene expression hallmarks of cellular ageing
Stephen Frenk,Jonathan Houseley +1 more
TL;DR: Six gene expression hallmarks of cellular ageing are identified, which encompass widely reported features of ageing such as increased senescence and inflammation, reduced electron transport chain activity and reduced ribosome synthesis, but also reveal a surprising lack of gene expression responses to known age-linked cellular stresses.
Journal ArticleDOI
The molecular basis of the organization of repetitive DNA-containing constitutive heterochromatin in mammals
Gohei Nishibuchi,Jérôme Déjardin +1 more
TL;DR: Ch Chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis is a powerful tool to investigate the epigenetic regulation of eukaryote genomes, but non-unique reads are usually discarded during standard ChIP- sequencing data alignment to reference genome databases, so specific methods to obtain global epigenetic information concerning repetitive elements are needed.
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.
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.