scholarly journals DNA damage response activation in mouse embryonic fibroblasts undergoing replicative senescence and following spontaneous immortalization

Cell Cycle ◽  
2008 ◽  
Vol 7 (22) ◽  
pp. 3601-3606 ◽  
Author(s):  
Raffaella Di Micco ◽  
Angelo Cicalese ◽  
Marzia Fumagalli ◽  
Miryana Dobreva ◽  
Alessandro Verrecchia ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Replicative Senescence ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Damage Response ◽  
Spontaneous Immortalization ◽  
Response Activation

scholarly journals Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation

2014 ◽  
Vol 21 (6) ◽  
pp. 998-1012 ◽  
Author(s):  
M Ogrunc ◽  
R Di Micco ◽  
M Liontos ◽  
L Bombardelli ◽  
M Mione ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Damage Response ◽  
Response Activation

Hepatitis B virus induces RNR-R2 expression via DNA damage response activation

2015 ◽  
Vol 63 (4) ◽  
pp. 789-796 ◽  
Author(s):  
Inna Ricardo-Lax ◽  
Vyas Ramanan ◽  
Eleftherios Michailidis ◽  
Tal Shamia ◽  
Nina Reuven ◽  
...  
Keyword(s):  
Dna Damage ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Damage Response ◽  
B Virus ◽  
Damage Response ◽  
Response Activation

scholarly journals What Lies in between Telomere and Organismal Ageing: Comparison between Replicative Senescence and Stress-Induced Premature Senescence

2021 ◽  
Vol 245 ◽  
pp. 03051
Author(s):  
Hanyi Jia
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Dna Damage Response ◽  
Replicative Senescence ◽  
Premature Senescence ◽  
Cycle Arrest ◽  
Damage Response ◽  
Permanent Cell ◽  
Stress Induced Premature Senescence

A mitotic cell that rests in permanent cell cycle arrest without the ability to divide is considered as a senescent cell. Cellular senescence is essential to limit the function of cells with heavy DNA damages. The lack of senescence is in favour of tumorigenesis, whereas the accumulation of senescent cells in tissues is likely to induce ageing and age-related pathologies on the organismal level. Understanding of cellular senescence is thus critical to both cancer and ageing studies. Senescence, essentially permanent cell cycle arrest, is one of the results of DNA damage response, such as the ataxia telangiectasia mutated and the ataxia telangiectasia and Rad3-related signaling pathways. In other cases, mild DNA damages can usually be repaired after DNA damage response, while the cells with heavy damages on DNA end in apoptosis. The damage to the special structure of telomere, however, prone to result in permanent cell cycle arrest after activation of DNA damage response. In fact, a few previous pieces of research on ageing have largely focused on telomere and considered it a primary contributor to different types of senescence. For instance, its reduction in length after each replication turns on a timer for replicative senescence, and its tandem repeats specific to binding proteins makes it susceptible to DNA damage from oxidative stress, and thus stress-induced premature senescence. In most of the senescent cells, the accumulation of biomarkers is found around the telomere which has either its tail structure disassembled or damage foci exposed on the tandem repeats. In this review, among several types of senescence, I will investigate two of the most common and widely discussed types in eukaryotic cells -replicative senescence and stress-induced premature senescence - in terms of their mechanism, relationship with telomere, and implication to organismal ageing.

scholarly journals Persistent telomere cohesion protects aged cells from premature senescence

2020 ◽  
Author(s):  
Kameron Azarm ◽  
Amit Bhardwaj ◽  
Eugenie Kim ◽  
Susan Smith
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Replicative Senescence ◽  
Protective Role ◽  
Premature Senescence ◽  
Telomere Shortening ◽  
Telomere Repeat ◽  
Gradual Loss ◽  
Damage Response ◽  
Tankyrase 1

AbstractHuman telomeres are bound by the telomere repeat binding proteins TRF1 and TRF2. Telomere shortening in human cells leads to a DNA damage response that signals replicative senescence. While insufficient loading of TRF2 at shortened telomeres contributes to the DNA damage response in senescence, the contribution of TRF1 to senescence induction has not been determined. Here we show that counter to TRF2 deficiency-mediated induction of DNA damage, TRF1 deficiency serves a protective role to limit induction of DNA damage induced by subtelomere recombination. Shortened telomeres recruit insufficient TRF1 and as a consequence inadequate tankyrase 1 to resolve sister telomere cohesion. The persistent cohesion protects short telomeres from inappropriate recombination. Ultimately, in the final division, telomeres are no longer able to maintain cohesion and subtelomere copying ensues. Thus, the gradual loss of TRF1 and concomitant persistent cohesion that occurs with telomere shortening ensures a measured approach to replicative senescence.

114 Chromatin modulates DNA damage response activation in oncogene-expressing cells

2009 ◽  
Vol 7 (2) ◽  
pp. 30
Author(s):  
F. D'adda Di Fagagna ◽  
R. Di Micco ◽  
G. Gargiulo ◽  
O. Botrugno ◽  
M. Fumagalli ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Damage Response ◽  
Response Activation

scholarly journals Centrosome Aberrations Associated with Cellular Senescence and p53 Localization at Supernumerary Centrosomes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Susumu Ohshima
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Cellular Senescence ◽  
Replicative Senescence ◽  
P53 Protein ◽  
Human Fibroblasts ◽  
Immunohistochemical Analysis ◽  
Premature Senescence ◽  
Damage Response ◽  
Mitotic Cells

Centrosome overduplication or amplification has been observed in many human cancers and in premalignant tissue, but the mechanisms leading to such centrosome aberrations are not fully understood. We previously showed that abnormal mitotic cells with supernumerary centrosomes increase with replicative senescence in human fibroblasts, especially in a polyploid subpopulation. This study examines localization of p53 protein at centrosomes in mitotic cells, which is often observed in association with DNA damage response, to investigate a possible association between p53 localization and numerical centrosome aberrations induced by cellular senescence. Cultures at later passages or the 4th day after exposure to H2O2showed increased frequencies of mitotic cells with supernumerary centrosomes, especially in a polyploid subpopulation. Immunohistochemical analysis frequently showed p53-positive foci in mitotic cells, and some were localized at centrosomes. The number of p53-positive foci in mitotic cells and its localization to centrosomes increased with replicative and premature senescence. Supernumerary centrosomes showed higher frequencies of p53 localization compared to normally duplicated centrosomes. Centrosome-associated p53 protein was phosphorylated at Ser15. These data suggest a possible association between localization of p53 protein and numerical centrosome aberrations in replicatively or prematurely senescent cells.

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