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
Role of senescence induction in cancer treatment.
TL;DR: A growing body of evidence has documented that senescence induction in tumor cells is a frequent response to many anticancer modalities including cyclin-dependent kinases 4/6 small molecule inhibitor-based targeted therapeutics and T helper-1 cytokine-mediated immunotherapy.
Journal ArticleDOI
Cellular senescence, epigenetic switches and c-Myc.
Isil Guney,John M. Sedivy +1 more
TL;DR: Findings point to the existence of a mechanism for monitoring hypoproliferative signaling, whose function may be to limit the proliferation and accretion of physiologically compromised cells, which may be another example of antagonistic pleiotropy leading to organismal aging.
Journal ArticleDOI
The retinoblastoma tumor suppressor protein is required for efficient processing and repair of trapped topoisomerase II-DNA-cleavable complexes.
Hai Xiao,David W. Goodrich +1 more
TL;DR: The functional status of pRb may influence sensitivity to etoposide by facilitating the repair of trapped TOP2–DNA complexes as well as by enforcing cell cycle checkpoints.
Journal ArticleDOI
Epigenetic Regulation of Cellular Senescence
Jack D. Crouch,Maria Shvedova,Rex Jeya Rajkumar Samdavid Thanapaul,Vladimir A. Botchkarev,Daniel S. Roh +4 more
TL;DR: This review will highlight the changes in chromatin, DNA methylation, and histone alterations that establish and maintain cellular senescence, alongside the specific epigenetic regulation of the senescENCE-associated secretory phenotype (SASP).
Journal ArticleDOI
Knockdown of inwardly rectifying potassium channel Kir2.2 suppresses tumorigenesis by inducing reactive oxygen species-mediated cellular senescence.
TL;DR: Knockdown of the inwardly rectifying K+ channel Kir2.2 induced growth arrest without additional cellular stress in cancer cells lacking functional p53, p16, and/or Rb, and it is proposed for the first time that Kir 2.2 knockdown induces senescence of cancer cells by a mechanism involving ROS accumulation that requires p27, but not Rb
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.