scholarly journals Yeast replicative aging leads to permanent cell cycle arrest in G1 effectuated by the start repressor Whi5

2018 ◽  
Author(s):  
Jing Yang ◽  
Ziwei Wang ◽  
Xili Liu ◽  
Hao Li ◽  
Qi Ouyang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Microfluidic Devices ◽  
Replicative Aging ◽  
Cycle Arrest ◽  
Permanent Cell ◽  
Response To Stress ◽  
Stress Signals ◽  
Mother Cells ◽  
Major Mediator

AbstractYeast replicative aging has been a canonical model for aging research. Since replicative aging eventually leads to permanent cell cycle arrest, a fundamental question is how cells sense the signals from aging and communicate that to the cell cycle control machineries. Using microfluidic devices to track individual mother cells labeled by two different cell cycle markers Whi5-tdTomato and Myo1-EGFP, we measured the length of different cell cycle phases as a function of age and the distribution of cell death in different cell cycle phases. We found that the majority of the cells died in the G1 phase, and their G1 cell cycle length increased drastically in the last few cell divisions. This increase of G1 length correlates with the increase of the nuclear concentration of Whi5, which is a major transcriptional suppressor of the cell cycle start check point. Interestingly, this correlation is apparent only above a threshold concentration of Whi5. We show that in response to external stress, Whi5 concentration increases and cell growth slows down in a Whi5 dependent manner, and that Whi5 deletion significantly extends the lifespan. Together these data suggest the existence of a programmed control to arrest cell cycle in G1 in response to stress signals due to aging, and that Whi5 is a major mediator of this process. Our findings may have important implications in understanding senescence and cancer in mammalian cells, which have a parallel G1/S control system with Rb (a well known tumor suppressor) as the analog of Whi5.Significance statementIn this work, we used microfluidic devices to track individual mother cells labeled by two cell cycle markers Whi5-tdTomato and Myo1-EGFP. We found that aging leads to significant lengthening of G1 phase in old cells and the eventual permanent cell cycle arrest in G1, and Whi5 plays an important role in implementing such a program. We show that oxidative stress can lead to the increase of Whi5 expression and the slow-down of cell division. Furthermore, Whi5 deletion significantly extends the lifespan. The result suggest the existence of a programmed control to arrest cell cycle in G1 in response to stress signals due to aging, and that Whi5 is a major mediator of this process.

scholarly journals A regulatory module controlling stress-induced cell cycle arrest in Arabidopsis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Naoki Takahashi ◽  
Nobuo Ogita ◽  
Tomonobu Takahashi ◽  
Shoji Taniguchi ◽  
Maho Tanaka ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Genotoxic Stress ◽  
Myb Transcription Factor ◽  
Protein Accumulation ◽  
G2 Arrest ◽  
Cycle Arrest ◽  
Regulatory Module ◽  
Stress Signals

Cell cycle arrest is an active response to stresses that enables organisms to survive under fluctuating environmental conditions. While signalling pathways that inhibit cell cycle progression have been elucidated, the putative core module orchestrating cell cycle arrest in response to various stresses is still elusive. Here we report that in Arabidopsis, the NAC-type transcription factors ANAC044 and ANAC085 are required for DNA damage-induced G2 arrest. Under genotoxic stress conditions, ANAC044 and ANAC085 enhance protein accumulation of the R1R2R3-type Myb transcription factor (Rep-MYB), which represses G2/M-specific genes. ANAC044/ANAC085-dependent accumulation of Rep-MYB and cell cycle arrest are also observed in the response to heat stress that causes G2 arrest, but not to osmotic stress that retards G1 progression. These results suggest that plants deploy the ANAC044/ANAC085-mediated signalling module as a hub which perceives distinct stress signals and leads to G2 arrest.

scholarly journals Chk1 and 14‐3‐3 proteins inhibit atypical E2Fs to prevent a permanent cell cycle arrest

2018 ◽  
Vol 37 (5) ◽  
Author(s):  
Ruixue Yuan ◽  
Harmjan R Vos ◽  
Robert M Es ◽  
Jing Chen ◽  
Boudewijn MT Burgering ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Permanent Cell

scholarly journals The Histone Code of Senescence

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 466 ◽  
Author(s):  
Harikrishnareddy Paluvai ◽  
Eros Di Giorgio ◽  
Claudio Brancolini
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Cellular Response ◽  
Premature Aging ◽  
Physiological Processes ◽  
Cycle Arrest ◽  
Damage Response ◽  
Permanent Cell ◽  
Second Wave

Senescence is the end point of a complex cellular response that proceeds through a set of highly regulated steps. Initially, the permanent cell-cycle arrest that characterizes senescence is a pro-survival response to irreparable DNA damage. The maintenance of this prolonged condition requires the adaptation of the cells to an unfavorable, demanding and stressful microenvironment. This adaptation is orchestrated through a deep epigenetic resetting. A first wave of epigenetic changes builds a dam on irreparable DNA damage and sustains the pro-survival response and the cell-cycle arrest. Later on, a second wave of epigenetic modifications allows the genomic reorganization to sustain the transcription of pro-inflammatory genes. The balanced epigenetic dynamism of senescent cells influences physiological processes, such as differentiation, embryogenesis and aging, while its alteration leads to cancer, neurodegeneration and premature aging. Here we provide an overview of the most relevant histone modifications, which characterize senescence, aging and the activation of a prolonged DNA damage response.

scholarly journals noxin, a Novel Stress-Induced Gene Involved in Cell Cycle and Apoptosis

2007 ◽  
Vol 27 (15) ◽  
pp. 5430-5444 ◽  
Author(s):  
Naoki Nakaya ◽  
Jill Hemish ◽  
Peter Krasnov ◽  
Sang-Yong Kim ◽  
Yuri Stasiv ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nuclear Localization Signals ◽  
Protein Levels ◽  
Cell Defense ◽  
Cycle Arrest ◽  
Wide Range ◽  
Dependent Protein ◽  
Response To Stress ◽  
Stress Signals ◽  
Inducible Gene

ABSTRACT We describe a novel stress-induced gene, noxin, and a knockout mouse line with an inactivated noxin gene. The noxin gene does not have sequelogs in the genome and encodes a highly serine-rich protein with predicted phosphorylation sites for ATM, Akt, and DNA-dependent protein kinase kinases; nuclear localization signals; and a Zn finger domain. noxin mRNA and protein levels are under tight control by the cell cycle. noxin, identified as a nitric oxide-inducible gene, is strongly induced by a wide range of stress signals: γ- and UV irradiation, hydrogen peroxide, adriamycin, and cytokines. This induction is dependent on p53. Noxin accumulates in the nucleus in response to stress and, when ectopically expressed, Noxin arrests the cell cycle at G1; although it also induces p53, the cell cycle arrest function of Noxin is independent of p53 activity. noxin knockout mice are viable and fertile; however, they have an enlarged heart, several altered hematopoietic parameters, and a decreased number of spermatids. Importantly, loss or downregulation of Noxin leads to increased cell death. Our results suggest that Noxin may be a component of the cell defense system: it is activated by various stress stimuli, helps cells to withdraw from cycling, and opposes apoptosis.

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.

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