scholarly journals Nucleosome remodelling, DNA repair and transcriptional regulation build negative feedback loops in cancer and cellular ageing

2017 ◽  
Vol 372 (1731) ◽  
pp. 20160473 ◽  
Author(s):  
Reiko Watanabe ◽  
Shin-ichiro Kanno ◽  
Amaneh Mohammadi Roushandeh ◽  
Ayako Ui ◽  
Akira Yasui
Keyword(s):  
Dna Repair ◽  
Transcriptional Regulation ◽  
Stem Cell ◽  
Cancer Cells ◽  
Negative Feedback ◽  
Feedback Loops ◽  
Dependent Manner ◽  
Epigenetic Changes ◽  
Negative Feedback Loops ◽  
Cellular Ageing

Nucleosome remodelling (NR) regulates transcription in an ATP-dependent manner, and influences gene expression required for development and cellular functions, including those involved in anti-cancer and anti-ageing processes. ATP-utilizing chromatin assembly and remodelling factor (ACF) and Brahma-associated factor (BAF) complexes, belonging to the ISWI and SWI/SNF families, respectively, are involved in various types of DNA repair. Suppression of several BAF factors makes U2OS cells significantly sensitive to X-rays, UV and especially to cisplatin, and these BAF factors contribute to the accumulation of repair proteins at various types of DNA damage and to DNA repair. Recent cancer genome sequencing and expression analysis has shown that BAF factors are frequently mutated or, more frequently, silenced in various types of cancer cells. Thus, those cancer cells are potentially X-ray- and especially cisplatin-sensitive, suggesting a way of optimizing current cancer therapy. Recent single–stem cell analysis suggests that mutations and epigenetic changes influence stem cell functionality leading to cellular ageing. Genetic and epigenetic changes in the BAF factors diminish DNA repair as well as transcriptional regulation activities, and DNA repair defects in turn negatively influence NR and transcriptional regulation. Thus, they build negative feedback loops, which accelerate both cellular senescence and transformation as common and rare cellular events, respectively, causing cellular ageing. This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.

Delay model of circadian gene expression with two negative feedback loops

2006 ◽  
Vol 37 (5) ◽  
pp. 405-417
Author(s):  
Andreas Bohn ◽  
José R. Lopes ◽  
Luís A. Diambra ◽  
Luiz S. Menna-Barreto
Keyword(s):  
Gene Expression ◽  
Negative Feedback ◽  
Feedback Loops ◽  
Delay Model ◽  
Circadian Gene ◽  
Negative Feedback Loops

scholarly journals Ionizing radiation induces stem cell-like properties in a caspase-dependent manner in Drosophila

2018 ◽  
Author(s):  
Shilpi Verghese ◽  
Tin Tin Su
Keyword(s):  
Stem Cell ◽  
Ionizing Radiation ◽  
Cancer Cells ◽  
Wing Disc ◽  
Lineage Tracing ◽  
Dependent Manner ◽  
Cancer Treatments ◽  
Therapeutic Success ◽  
Wing Discs ◽  
Regenerative Cells

ABSTRACTCancer treatments including ionizing radiation (IR) can induce cancer stem cell-like properties in non-stem cancer cells, an outcome that can interfere with therapeutic success. Yet, we understand little about what consequences of IR induces stem cell like properties and why some cancer cells show this response but not others. In previous studies, we identified a pool of epithelial cells in Drosophila larval wing discs that display IR-induced stem cell-like properties. These cells are resistant to killing by IR and, after radiation damage, change fate and translocate to regenerate parts of the disc that suffered more cell death. Here, we addressed how IR exposure results in the induction of stem cell-like behavior, and found a requirement for caspase activity. Unexpectedly, this requirement was mapped to the regenerative cells, suggesting a non-apoptotic role for caspases in the induction of stem cell-like behavior. We also performed a systematic probing of different regions of the wing disc by lineage tracing, in order to identify additional pools of cells with IR-induced regenerative properties. We identified two new populations of such cells. Unlike the original pool that helps regenerate the disc, the new pools of cells undergo abnormal regeneration to produce an ectopic, supernumerary wing disc. We also identified cells that lack the ability to display IR-induced regenerative behavior. Identification of different cell populations with different IR-induced regenerative potential will allow us to probe the molecular basis for these differences in the future.AUTHOR SUMMARYIonizing Radiation (IR), alone or in combination with other therapies, is used to treat an estimated half of all cancer patients. Yet, we understand little about why some tumors cells respond to treatment while others grow back (regenerate). We identified specific pools of cells within a Drosophila organ that are capable of regeneration after damage by IR. We also identified what it is about IR damage that allows these cells to regenerate. These results help us understand how cells regenerate after IR damage and will aid in designing better therapies that involve radiation.

scholarly journals Limit cycles in models of circular gene networks regulated by negative feedback loops

2020 ◽  
Vol 21 (S11) ◽  
Author(s):  
Vitaly A. Likhoshvai ◽  
Vladimir P. Golubyatnikov ◽  
Tamara M. Khlebodarova
Keyword(s):  
Negative Feedback ◽  
Gene Networks ◽  
Functional Organization ◽  
Molecular Genetic ◽  
Feedback Loops ◽  
System Structure ◽  
Signal Delay ◽  
Negative Feedback Loops ◽  
Regulatory Signal ◽  
Delay Phenomenon

Abstract Background The regulatory feedback loops that present in structural and functional organization of molecular-genetic systems and the phenomenon of the regulatory signal delay, a time period between the moment of signal reception and its implementation, provide natural conditions for complicated dynamic regimes in these systems. The delay phenomenon at the intracellular level is a consequence of the matrix principle of data transmission, implemented through the rather complex processes of transcription and translation.However, the rules of the influence of system structure on system dynamics are not clearly understood. Knowledge of these rules is particularly important for construction of synthetic gene networks with predetermined properties. Results We study dynamical properties of models of simplest circular gene networks regulated by negative feedback mechanisms. We have shown existence and stability of oscillating trajectories (cycles) in these models. Two algorithms of construction and localization of these cycles have been proposed. For one of these models, we have solved an inverse problem of parameters identification. Conclusions The modeling results demonstrate that non-stationary dynamics in the models of circular gene networks with negative feedback loops is achieved by a high degree of non-linearity of the mechanism of the autorepressor influence on its own expression, by the presence of regulatory signal delay, the value of which must exceed a certain critical value, and transcription/translation should be initiated from a sufficiently strong promoter/Shine-Dalgarno site. We believe that the identified patterns are key elements of the oscillating construction design.

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