Relevant bibliographies by topics / Genotoxic stress response

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  1. Journal articles
  2. Dissertations / Theses
  3. Books
  4. Book chapters
  5. Conference papers

Academic literature on the topic 'Genotoxic stress response'

Author: Grafiati
Published: 6 September 2023

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Journal articles on the topic "Genotoxic stress response"

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Antoch, Marina P., and Roman V. Kondratov. "Circadian Proteins and Genotoxic Stress Response." Circulation Research 106, no. 1 (January 8, 2010): 68–78. http://dx.doi.org/10.1161/circresaha.109.207076.

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Chen, Ting-Yu, Bu-Miin Huang, Tang K. Tang, Yu-Ying Chao, Xiao-Yi Xiao, Pei-Rong Lee, Li-Yun Yang, and Chia-Yih Wang. "Genotoxic stress-activated DNA-PK-p53 cascade and autophagy cooperatively induce ciliogenesis to maintain the DNA damage response." Cell Death & Differentiation 28, no. 6 (January 18, 2021): 1865–79. http://dx.doi.org/10.1038/s41418-020-00713-8.

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AbstractThe DNA-PK maintains cell survival when DNA damage occurs. In addition, aberrant activation of the DNA-PK induces centrosome amplification, suggesting additional roles for this kinase. Here, we showed that the DNA-PK-p53 cascade induced primary cilia formation (ciliogenesis), thus maintaining the DNA damage response under genotoxic stress. Treatment with genotoxic drugs (etoposide, neocarzinostatin, hydroxyurea, or cisplatin) led to ciliogenesis in human retina (RPE1), trophoblast (HTR8), lung (A459), and mouse Leydig progenitor (TM3) cell lines. Upon genotoxic stress, several DNA damage signaling were activated, but only the DNA-PK-p53 cascade contributed to ciliogenesis, as pharmacological inhibition or genetic depletion of this pathway decreased genotoxic stress-induced ciliogenesis. Interestingly, in addition to localizing to the nucleus, activated DNA-PK localized to the base of the primary cilium (mother centriole) and daughter centriole. Genotoxic stress also induced autophagy. Inhibition of autophagy initiation or lysosomal degradation or depletion of ATG7 decreased genotoxic stress-induced ciliogenesis. Besides, inhibition of ciliogenesis by depletion of IFT88 or CEP164 attenuated the genotoxic stress-induced DNA damage response. Thus, our study uncovered the interplay among genotoxic stress, the primary cilium, and the DNA damage response.
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Dbaibo, G. S., M. Y. Pushkareva, R. A. Rachid, N. Alter, M. J. Smyth, L. M. Obeid, and Y. A. Hannun. "p53-dependent ceramide response to genotoxic stress." Journal of Clinical Investigation 102, no. 2 (July 15, 1998): 329–39. http://dx.doi.org/10.1172/jci1180.

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Shi, Qing-Mei, Yan-Ming Wang, Xin-De Zheng, Raymond Teck Ho Lee, and Yue Wang. "Critical Role of DNA Checkpoints in Mediating Genotoxic-Stress–induced Filamentous Growth inCandida albicans." Molecular Biology of the Cell 18, no. 3 (March 2007): 815–26. http://dx.doi.org/10.1091/mbc.e06-05-0442.

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The polymorphic fungus Candida albicans switches from yeast to filamentous growth in response to a range of genotoxic insults, including inhibition of DNA synthesis by hydroxyurea (HU) or aphidicolin (AC), depletion of the ribonucleotide-reductase subunit Rnr2p, and DNA damage induced by methylmethane sulfonate (MMS) or UV light (UV). Deleting RAD53, which encodes a downstream effector kinase for both the DNA-replication and DNA-damage checkpoint pathways, completely abolished the filamentous growth caused by all the genotoxins tested. Deleting RAD9, which encodes a signal transducer of the DNA-damage checkpoint, specifically blocked the filamentous growth induced by MMS or UV but not that induced by HU or AC. Deleting MRC1, the counterpart of RAD9 in the DNA-replication checkpoint, impaired DNA synthesis and caused cell elongation even in the absence of external genotoxic insults. Together, the results indicate that the DNA-replication/damage checkpoints are critically required for the induction of filamentous growth by genotoxic stress. In addition, either of two mutations in the FHA1 domain of Rad53p, G65A, and N104A, nearly completely blocked the filamentous-growth response but had no significant deleterious effect on cell-cycle arrest. These results suggest that the FHA domain, known for its ability to bind phosphopeptides, has an important role in mediating genotoxic-stress–induced filamentous growth and that such growth is a specific, Rad53p-regulated cellular response in C. albicans.
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Sun, X., H. Shimizu, and K. Yamamoto. "Identification of a novel p53 promoter element involved in genotoxic stress-inducible p53 gene expression." Molecular and Cellular Biology 15, no. 8 (August 1995): 4489–96. http://dx.doi.org/10.1128/mcb.15.8.4489.

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p53 is recruited in response to DNA-damaging genotoxic stress and plays an important role in maintaining the integrity of the genome. We show that exposure of cells to various genotoxic agents, including anticancer drugs such as mitomycin and 5-fluorouracil, results in an increase in p53 mRNA levels and in p53 promoter activation, indicating that the p53 genotoxic stress response is partly regulated at the transcriptional level. The results of the p53 promoter analysis show that a novel p53 promoter element, termed a p53 core promoter element (from -70 to -46), is essential for basal p53 promoter activity and promoter activation induced by genotoxic agents such as anticancer drugs and UV. Although a kappa B motif partially overlaps with this element and those genotoxic agents activate NF-kappa B, it does not play a major role in p53 genotoxic stress response: NF-kappa B p65 expression did not induce significant p53 promoter activation, and NF-kappa B inhibitors (N-acetyl cysteine and I kappa B alpha) did not inhibit genotoxic stress-inducible p53 promoter activation. Finally, we characterized nuclear factors, the binding of which to the p53 core promoter element is essential for basal p53 promoter activity and p53 promoter activation induced by genotoxic agents.
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Liu, Li, Jiri Veis, Wolfgang Reiter, Edwin Motari, Catherine E. Costello, John C. Samuelson, Gustav Ammerer, and David E. Levin. "Regulation of Pkc1 Hyper-Phosphorylation by Genotoxic Stress." Journal of Fungi 7, no. 10 (October 17, 2021): 874. http://dx.doi.org/10.3390/jof7100874.

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The cell wall integrity (CWI) signaling pathway is best known for its roles in cell wall biogenesis. However, it is also thought to participate in the response to genotoxic stress. The stress-activated protein kinase Mpk1 (Slt2, is activated by DNA damaging agents through an intracellular mechanism that does not involve the activation of upstream components of the CWI pathway. Additional observations suggest that protein kinase C (Pkc1), the top kinase in the CWI signaling cascade, also has a role in the response to genotoxic stress that is independent of its recognized function in the activation of Mpk1. Pkc1 undergoes hyper-phosphorylation specifically in response to genotoxic stress; we have found that this requires the DNA damage checkpoint kinases Mec1 (Mitosis Entry Checkpoint) and Tel1 (TELomere maintenance), but not their effector kinases. We demonstrate that the casein kinase 1 (CK1) ortholog, Hrr25 (HO and Radiation Repair), previously implicated in the DNA damage transcriptional response, associates with Pkc1 under conditions of genotoxic stress. We also found that the induced association of Hrr25 with Pkc1 requires Mec1 and Tel1, and that Hrr25 catalytic activity is required for Pkc1-hyperphosphorylation, thereby delineating a pathway from the checkpoint kinases to Pkc1. We used SILAC mass spectrometry to identify three residues within Pkc1 the phosphorylation of which was stimulated by genotoxic stress. We mutated these residues as well as a collection of 13 phosphorylation sites within the regulatory domain of Pkc1 that fit the consensus for CK1 sites. Mutation of the 13 Pkc1 phosphorylation sites blocked hyper-phosphorylation and diminished RNR3 (RiboNucleotide Reductase) basal expression and induction by genotoxic stress, suggesting that Pkc1 plays a role in the DNA damage transcriptional response.
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Suh, Yousin, Kang-Ae Lee, Woo-Ho Kim, Bok-Ghee Han, Jan Vijg, and Sang Chul Park. "Aging alters the apoptotic response to genotoxic stress." Nature Medicine 8, no. 1 (January 2002): 3–4. http://dx.doi.org/10.1038/nm0102-3.

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Dutertre, Martin, Gabriel Sanchez, Marie-Cécile De Cian, Jérôme Barbier, Etienne Dardenne, Lise Gratadou, Gwendal Dujardin, Catherine Le Jossic-Corcos, Laurent Corcos, and Didier Auboeuf. "Cotranscriptional exon skipping in the genotoxic stress response." Nature Structural & Molecular Biology 17, no. 11 (October 24, 2010): 1358–66. http://dx.doi.org/10.1038/nsmb.1912.

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FORNACE, ALBERT J., JOANY JACKMAN, M. CHRISTINE HOLLANDER, BARBARA HOFFMAN-LIEBERMANN, and DAN A. LIEBERMANN. "Genotoxic-Stress-Response Genes and Growth-Arrest Genes." Annals of the New York Academy of Sciences 663, no. 1 Aging and Cel (November 1992): 139–53. http://dx.doi.org/10.1111/j.1749-6632.1992.tb38657.x.

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Kumari, Nidhi, M. Abul Hassan, Xiangdong Lu, Robert G. Roeder, and Debabrata Biswas. "AFF1 acetylation by p300 temporally inhibits transcription during genotoxic stress response." Proceedings of the National Academy of Sciences 116, no. 44 (October 14, 2019): 22140–51. http://dx.doi.org/10.1073/pnas.1907097116.

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Soon after exposure to genotoxic reagents, mammalian cells inhibit transcription to prevent collisions with repair machinery and to mount a proper DNA damage response. However, mechanisms underlying early transcriptional inhibition are poorly understood. In this report, we show that site-specific acetylation of super elongation complex (SEC) subunit AFF1 by p300 reduces its interaction with other SEC components and impairs P-TEFb−mediated C-terminal domain phosphorylation of RNA polymerase II both in vitro and in vivo. Reexpression of wild-type AFF1, but not an acetylation mimic mutant, restores SEC component recruitment and target gene expression in AFF1 knockdown cells. Physiologically, we show that, upon genotoxic exposure, p300-mediated AFF1 acetylation is dynamic and strongly correlated with concomitant global down-regulation of transcription—and that this can be reversed by overexpression of an acetylation-defective AFF1 mutant. Therefore, we describe a mechanism of dynamic transcriptional regulation involving p300-mediated acetylation of a key elongation factor during genotoxic stress.
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Dissertations / Theses on the topic "Genotoxic stress response"

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Konstantinidou, C. "Stage-specific response of NC lineages to genotoxic stress." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1458881/.

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The enteric nervous system (ENS) constitutes a gut-intrinsic network of interconnected ganglia which control multiple aspects of gastrointestinal activity, including motility, secretion and blood flow. Most enteric neurons and glia are derived from a relatively small population of neural crest (NC) cells which originate primarily from the vagal NC and migrate ventromedially to invade the foregut mesenchyme. Within the gut microenvironment, ENS progenitors receive signals that allow them to survive, proliferate, differentiate and migrate extensively, giving rise to a uniformly distributed population of enteric neurons and glia. So far, most developmental studies have explored the behaviour of ENS progenitors within the gut wall, but little is known about the properties of NC cells prior to foregut invasion. To explore the spatiotemporal dynamics of ENS development, we conditionally inactivated Geminin (Gem), a mouse gene with fundamental roles in genome integrity and cell fate decisions. Gem deletion from pre-enteric NC cells results in extensive DNA damage followed by P53-mediated apoptotic cell death and intestinal aganglionosis. In contrast, ablation of Gem from enteric NC cells has minimal effects on ENS development. To determine whether ENS lineages display a stage-specific sensitivity to generic genotoxic stress, we monitored the in vivo response of NC cells to γ-irradiation at different developmental stages. While both pre-enteric and enteric NC cells where characterised by robust DNA damage response, pre-enteric NC cells displayed a far greater apoptotic response relative to their enteric counterparts. These experiments reveal a previously unknown spatiotemporal sensitivity of NC cell lineages to genotoxic stress and provide an experimental paradigm for understanding the mechanisms by which DNA damage from genetic or environmental insults leads to congenital ENS deficits. Our studies allow us to draw general conclusions as to how DNA damage and fundamental developmental processes are integrated in vertebrate embryos.
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Purmessur, Nadia Sheree. "The regulation of p53-dependent microRNA expression in response to genotoxic stress." Thesis, University of Leicester, 2014. http://hdl.handle.net/2381/28637.

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Introduction: miR-16 and miR-26a have been identified as key effectors of the p53 pathway in response to genotoxic stress. This work is focused on preliminary elucidation of regulatory mechanisms by which p53 controls expression of miR-16 and miR-26a and characterisation of their gene targets involved in the p53 network. Methods: Microarray expression analysis of miR-16 and miR-26a was followed by Q-PCR to confirm these miRNAs dependence on p53. We analysed the transcriptional regulation of these miRNAs by p53 via luciferase assay and ChIP assay. We investigated these miRNAs contribution to p53-dependent response to genotoxic stress. To validate miR-16 and miR-26a targets (Cyclin E, CHK1, and WEE1) we employed Q-PCR, western blotting and luciferase assay. We also analysed the transcriptional regulation of Cyclin E by SET9 via luciferase assay. Results: High miR-16 and miR-26a expression are associated with increased cancer survival. p53-dependent and -independent regulatory mechanisms exist for miR-16 and miR-26a, and p53 controls expression of miRNAs on several levels. p53 recruits Drosha complex to miR-16 and miR-26a to facilitate the processing of these miRNAs. miR-26a cooperates with p53 to induce apoptosis and miR-16 enhances p53-mediated cell cycle arrest. miR-16 and miR-26a regulates CHK1 and WEE1, in the presence or absence of p53. miR-16 also reduces Cyclin E levels, in the presence and absence of p53. SET9 controls expression of Cyclin E on a transcriptional level. Conclusions: Our results showed that in response to DNA damage, miR-16 and miR-26a expression levels are controlled by p53-dependent and p53-independent mechanisms, potentially involving other stress-response transcription factors such as E2F1. Our data also confirms that miR-16 and miR-26a directly target Cyclin E, CHK1, and WEE1 for down-regulation. Additonally, SET9 directly controls Cyclin E expression. Reduced CHK1 and WEE1 levels leads to decreased G2/M arrest, and reduced Cyclin E levels results in increased G1/S arrest. As a consequence, apoptosis occurs.
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Vickridge, Elise. "Management of E. coli sister chromatid cohesion in response to genotoxic stress." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS172/document.

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La réplication fidèle de l’ADN au cours du cycle cellulaire est essentielle au maintien de l’intégrité du génome à travers les générations. Toutefois, de nombreux éléments peuvent perturber et compromettre la réplication et donc cette intégrité. La mitomycine C (MMC) est une molécule génotoxique utilisée en chimiothérapie. Elle forme des liaisons covalentes entre les deux brins d’ADN, ce qui est un obstacle à la bonne réplication de l’ADN. La rencontre de la fourche de réplication avec une liaison covalente entre les deux brins d’ADN va aboutir à une cassure double brin. Escherichia coli (E.coli) est un modèle d’étude très étendu car facile d’utilisation, permettant d’aborder des notions complexes. E coli possède divers mécanismes pour réparer ces lésions dont le régulon SOS. Le régulon SOS est un ensemble de gènes sous contrôle d’un promoteur réprimé par la protéine LexA. En réponse à des dommages à l’ADN, LexA est dégradé et les gènes du régulon sont activés.En utilisant une technique de biologie moléculaire qui permet de quantifier l’interaction entre deux chromatides sœurs restées cohésives derrière la fourche de réplication (étape appelée cohésion des chromatides sœurs), nous avons montré qu’en réponse à des cassures double brin générées par la MMC, la cohésion entre les chromatides sœurs nouvellement répliquées est maintenue. Ce phénomène est dépendant de RecN, une protéine induite de façon précoce dans le régulon SOS. RecN est une protéine de type SMC (structural maintenance of chromosomes), un groupe de protéines impliqué dans la dynamique et la structure du chromosome. En parallèle, des techniques de microscopie confocale et de marquage du chromosome par des protéines fluorescentes ont permis de montrer que la protéine RecN est impliquée dans une condensation globale du nucléoide suite à un traitement par la MMC. Cette condensation du nucléoide s’accompagne d’un rapprochement des chromatides sœurs ségrégées. Ces deux phénomènes, médiés par RecN pourraient permettre une stabilisation globale des nucléoides et favoriser l’appariement des chromatides sœurs pour permettre la recombinaison homologue.De façon intéressante, l’inhibition de Topoisomérases de type II (Topoisomerase IV et Gyrase) permettent de restaurer le phénotype d’un mutant recN en viabilité et en cohésion des chromatides sœurs. Les Topoisomérases sont des protéines qui prennent en charge les liens topologiques générés par la réplication et la transcription). Les liens topologiques non éliminés par les Topoisomerases permettraient de garder les chromatides sœurs cohésives et favoriser la réparation, même en l’absence de RecN.De plus, une expérience de RNA seq (séquençage de tout le transcriptome de la bactérie) a révélé que dans un mutant recN, le régulon SOS est moins induit que dans les cellules sauvages. Ceci va de pair avec une déstructuration des foci de réparation RecA. Il est possible que le rapprochement des chromatides sœurs médié par RecN permettrait de stabiliser le filament RecA et donc l’induction du SOS.L’ensemble de ces résultats suggère que RecN, une protéine de type SMC, permet de maintenir la cohésion entre les chromatides sœurs nouvellement répliquées, favorisant la réparation de cassures double brins par recombinaison homologue
Maintaining genome integrity through replication is an essential process for the cell cycle. However, many factors can compromise this replication and thus the genome integrity. Mitomycin C is a genotoxic agent that creates a covalent link between the two DNA strands. When the replication fork encounters the DNA crosslink, it breaks and creates a DNA double strand break (DSB). Escherichia coli (E.coli) is a widely used model for studying complex DNA mechanisms. When facing a DNA DSB, E. coli activates the SOS response pathway. The SOS response comprises over 50 genes that are under the control of a LexA-repressed promoter. Upon a DSB induction, RecA, a central protein of the SOS response will trigger the degradation of LexA and all the SOS genes will be expressed.We have developed a novel molecular biology tool that reveals contacts between sister chromatids that are cohesive. It has been shown in the lab (Lesterlin et al. 2012) that during a regular cell cycle, the two newly replicated sister chromatids stay in close contact for 10 to 20 min before segregating to separate cell halves thanks to the action of Topoisomerase IV. This step is called sister chromatid cohesion. We have used this molecular biology tool to study sister chromatid cohesion upon a genotoxic stress induced by mitomycin C (MMC). We have shown that sister chromatid cohesion is maintained and prolonged when the cell is facing a DSB. Moreover, this sister chromatid cohesion is dependent on RecN, an SOS induced structural maintenance of chromosome-like (SMC-like) protein. In the absence of RecN, the proximity between both sister chromatids is lost and this has a deleterious effect on cell viability. By tagging the chromosome with fluorescent proteins, we have revealed that RecN can also mediated a progressive regression of two previously segregated sister chromatids and this is coordinated with a whole nucleoid compaction. Further studies showed that this genome compaction is orderly and is not the result of a random compaction in response to DNA damage.Interestingly, inhibiting TopoIV in a recN mutant fully restores viability and sister chromatid cohesion suggesting that RecN’s action is mainly structural. Preserving cohesion through precatenanes is sufficient to favor repair and cell viability even in the absence of RecN.An RNA-seq experiment in a WT strain and a recN mutant revealed that the whole SOS response is downregulated in a recN mutant. This suggests that RecN may have an effect on the induction of the SOS response and thus RecA filament formation. This is in good agreement with the change in RecA-mcherry foci formation we observed. In the WT strain, the RecA-mcherry foci are defined as described in previous work. However, in the recN, the RecA-mcherry foci seemed to form bundle like structures. These RecA bundles were previsously described by Lesterlin et al. in the particular case of a DSB occurring on a chromatid that has already been segregated from its homolog. This could mean that in the absence of recN, the sister chromatids segregate and RecA forms bundle like structures in order to perform a search for the intact homologous sister chromatid.Altogether, these results reveal that RecN is an essential protein for sister chromatid cohesion upon a genotoxic stress. RecN favors sister chromatid cohesion by preventing their segregation. Through a whole nucleoid rearrangement, RecN mediates sister chromatid regression, favoring DNA repair and cell viability
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Davidson, Adam. "Investigating the Role of Interferon Regulatory Factor 3 in Response to Genotoxic Stress." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/24928.

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Interferon regulatory factor 3 (IRF3) plays an important role in activating the innate immune response in a variety of conditions, including viral infection. As well as regulating the immune response to viruses, IRF3 is involved in regulating cellular functions including apoptosis. Apoptosis and the inflammatory response to viral infection are very different; therefore, it is obvious that IRF3 plays dramatically different roles in the cell depending on the conditions. We previously identified a non-activating phosphorylation of IRF3 in response to adenovirus (Ad) in which Serine-173 is phosphorylated. In addition to Ad infection, IRF3- S173 is phosphorylated in response to genotoxic stresses including ultraviolet (UV) irradiation and etoposide. In this study, I show that this phosphorylation event is involved in a variety of processes including protein stability, cell survival and IRF3 regulation. Thus, phosphorylation of IRF3-S173 is a novel and important event in a complex regulatory pathway of an integral protein.
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Liu, Jia, and 劉佳. "Role of FBXO31 in regulating MAPK-mediated genotoxic stress response and cancer cell survival." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/205657.

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Esophageal cancer is the third most common digestive tract malignancy. Along with surgery, genotoxic drugs (e.g. cisplatin) and radiotherapy are the mainstays of treatment for this disease. Environmental factors and environmental stress-induced responses contribute to esophageal tumorigenesis and chemoresistance. Studying key molecules in stress-induced signal pathway can help unravel the underlying mechanisms and discover rational therapeutic targets. Cyclin D1 is DNA damage response protein. Genotoxic stress induces rapid cyclin D1 degradation and the molecules mediating this response are cell-type dependent. The first part of this study investigated the changes of cyclin D1 expression in response to genotoxic stress in immortalized esophageal epithelial cells, which are experimental models commonly used to study the early events of cancer development. The results showed that cyclin D1 underwent rapid proteasomal degradation before p53-induced p21 accumulation, which substantiates that cyclin D1 plays a role in eliciting cell cycle arrest very early in the DNA damage response. FBXO31 and FBX4, two F-box proteins previously reported to mediate cyclin D1 degradation, were found to be accumulated and unchanged, respectively, after ionizing irradiation in immortalized esophageal epithelial cells and esophageal squamous cell carcinoma (ESCC) cell lines. Yet, knockdown of FBXO31 did not rescue rapid cyclin D1 degradation upon UV or ionizing irradiation. This led to the hypothesis that accumulation of FBXO31 may have novel functions beyond mediating cyclin D1 degradation in cells responding to genotoxic stress. The second part of this study explored the function of FBXO31 in genotoxic stress response. The accumulation of FBXO31 in cancer cells after exposure to various genotoxic stresses was found to coincide with p38 deactivation, giving the clue that FBXO31 may negatively regulate this important pathway. Further studies revealed that knockdown of FBXO31 resulted in sustained activation of stress-activated MAPKs (SAPKs) p38 and JNK, as well as increase in UV-induced cell apoptosis, whereas overexpression of FBXO31 had opposite effects. The inhibitory role of FBXO31 on SAPK activation and apoptosis was confirmed by shRNA rescue experiments. Consistent with the observed anti-apoptotic effect, soft agar, colony formation and in vivo xenograft experiments showed that FBXO31 had oncogenic function in ESCC. Moreover, in vitro and in vivo results showed that knockdown of FBXO31 could sensitize ESCC cells to cisplatin treatment. The mechanism underlying the inhibition of SAPKs by FBXO31 was investigated in the third part of this study. Co-immunoprecipitation results showed that FBXO31 could interact with MKK6 (a p38 activator), but not p38, JNK1, or other MAP2Ks. FBXO31 was found to be co-localized with MKK6 in the cytoplasm. Mapping of interaction domains of FBXO31 revealed that aa 115-240 and aa 351-475 were responsible for binding to MKK6. Further study found that binding of FBXO31 to MKK6 could facilitate the K48-linked polyubiquitination and degradation of MKK6. Taken together, the results of this study showed that FBXO31 accumulation upon genotoxic stress can promote the degradation of MKK6 via K48-linked ubiquitination, thereby inhibiting SAPK activation and protecting cancer cells from genotoxic stress-induced apoptosis. FBXO31 may be a potentially useful therapeutic target to overcome chemoresistance in cancer therapy.
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Al-Asadi, Mazin Gh. "Investigation of dormancy in acute myeloid leukaemia cells and the induction of dormancy in their response to genotoxic stress." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/43320/.

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Cancer cells can exist in a reversible state of dormancy (G0 phase of the cell cycle). Relapse of acute myeloid leukaemia (AML) is likely due to dormant cells escape frontline treatment. Dormant AML cells have been identified in the bone marrow (BM) endosteal region which is characterised by an excess of TGFβ1 and a shortage of nutrients. As the first step in this project, we developed an in vitro model of AML cell dormancy by exploiting these features. Following a preliminary investigation of four AML cell lines, the CD34+CD38- line TF1-a was selected for in-depth investigation. TF1-a showed significant inhibition of proliferation, with features of dormancy and stemness, in response to 72 hours of TGFB1+mTOR inhibitor treatment (mTOR pathway inhibition mimics major effects of nutrient scarcity) without affecting cell viability or inducing differentiation of these cells. Secondly, whole human genome gene expression profiling using Affymetrix microarray strips (HuGene2.1ST) was conducted to molecularly characterise the dormancy-induced TF1-a cells. As a result, we identified 240 genes which were significantly up-regulated by at least twofold, including genes involved in adhesion, stemness, chemoresistance, tumor suppression and genes involved in canonical cell cycle regulation. The most upregulated gene was osteopontin (17.1fold). Immunocytochemistry of BM biopsies from AML patients confirmed high levels of osteopontin in the cytoplasm of blasts near the paratrabecular BM. Osteopontin and other genes identified in this model, including well-characterised genes (e.g. CD44, CD47, CD123, ABCC3 and CDKN2B) as well as little-known ones (e.g. ITGB3, BTG2 and PTPRU), are potential therapeutic targets in AML. AML cells which are identified in the bone marrow (BM) endosteal region are likely to survive chemotherapy for several reasons including the low concentration of the drug delivered to this poorly perfused area of the BM. We hypothesised that these cells might induce dormancy features that help them escaping chemotherapy. Moreover, little is known regarding the molecular changes in those AML cells surviving genotoxic stress. The third aim of this study was to investigate the AML cells surviving genotoxic stress. Therefore, we developed and characterised an in vitro model of prolonged sub-lethal genotoxicity in AML cells by utilising the TF1-a cells treated with etoposide for 6 days. TF1-a cells survived this conditioning with significant inhibition of proliferation and limited damage and apoptosis. The molecular signature of these cells was characterized using GEP of the whole human genome and was compared to that of the dormancy-induced TF1-a cells in an aim to identify genes commonly up-regulated in both scenarios that might act as possible drivers of dormancy in AML cells residing in a sub-lethal genotoxic environment. In this context, 31 genes were significantly commonly upregulated in both scenarios including ITGB3, SLFN5, C15orf26 and GRAP2 which are candidates for in-depth investigation in AML. To sum up, in this study we developed and molecularly characterised in vitro models of dormancy and sub-lethal genotoxicity in AML cells with stemness characteristics through novel approaches that took bone marrow microenvironmental features into consideration. These features likely contribute to the resistance of the residual sub-population of AML cells that causing disease relapse. The current models helped to overcome the obstacles facing the in-depth studying of these rare AML cells due to the difficulty in obtaining them from clinical samples. Finally, the molecular findings of this study paved the way to potentially important future directions of research that could help to achieve the ultimate goal of eradicating AML cells and preventing relapse.
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Stockwell, Simon Reidar. "The role of threonine 286 phosphorylation on cyclin D1 in sub-cellular localisation and proteolysis in response to genotoxic stress." Thesis, Institute of Cancer Research (University Of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406688.

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Duarte, Alexandra. "The interplay between MYCN and the DNA damage response : modulation of MYCN expression, its interactions with components of the DNA damage response and cellular responses to N-myc following genotoxic stress." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/9832.

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The DNA damage response (DDR) forms a signaling cascade rapidly activated upon exposure to genotoxic stress. The DDR safeguards genomic integrity by halting cell cycle progression to allow repair of damaged DNA or by inducing cell death. Myc proteins are key regulators of cell proliferation that transcriptionally control the cell cycle machinery. Amplification of N-myc in neuroblastomas (MNA-NB) is associated with abrogation of the regulatory mechanisms that normally prevent aberrant cell proliferation and the interplay between N-myc and the DDR was here analysed. Initially, an association between N-myc and the cdk inhibitor p21 was investigated in MNA-NB as a possible mechanism by which p21 is functionally suppressed in these cells. Although an N-myc/p21 interaction was not observed, MNA-NB cells appear to express short N-myc isoforms with the potential to associate with p21. Expression of N-myc rendered Rat-1 cells resistant to the cell cycle block imposed by serum starvation but these cells were not able to bypass a G1 arrest imposed by ectopic p21 suggesting N-myc does not abolish p21 activity through regulation at the protein level. Analysis of the N-myc response to DNA damage in MNA-NB cells revealed that N-myc is downregulated in a proteasome-dependent manner in response to UVC or a UV-mimetic carcinogen, 4NQO. This effect was not reproduced with other agents such as IR which like UVC were found to repress cyclin D1 expression likely indicating that alternative DDR signaling pathways differently regulate N-myc. N-myc was found to interact with the DDB2 subunit of the damaged-DNA binding (DDB) complex, a substrate receptor for the DDB1-Cul4ADDB2 E3 ligase. The DDB complex has been implicated in UV-induced protein ubiquitylation suggesting it may play a role in the N-myc response to UVC radiation. These findings highlight the complexities of the DDR and uncover potentially important mechanisms of cell cycle control through regulation of N-myc.
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Cook, Peter Joseph. "Eya a dual function nuclear factor crucial for regulation of developmental gene expression and prevention of apoptosis in response to genotoxic stress /." Diss., [La Jolla, Calif.] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3344509.

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Thesis (Ph. D.)--University of California, San Diego, 2009.
Title from first page of PDF file (viewed March 13, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Tomkins, C. E. "Cellular responses to genotoxic stress." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362104.

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Books on the topic "Genotoxic stress response"

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Grewal, Mandeep Kaur. ARAP2 is induced in response to genotoxic stress and B cell stimulation. 2005.

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Laposa, Rebecca Rachelle. The role of DNA repair and genotoxic stress responses in xenobiotic-initiated teratogenesis. 2001.

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Laposa, Rebecca Rachelle. The role of DNA repair and genotoxic stress responses in xenobiotic-initiated teratogenesis. 2001.

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Book chapters on the topic "Genotoxic stress response"

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Holbrook, N. J., Y. Liu, and A. J. Fornace. "Signaling events controlling the molecular response to genotoxic stress." In Stress-Inducible Cellular Responses, 273–88. Basel: Birkhäuser Basel, 1996. http://dx.doi.org/10.1007/978-3-0348-9088-5_18.

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Macovei, Anca, Mattia Donà, Daniela Carbonera, and Alma Balestrazzi. "Plant Response to Genotoxic Stress: A Crucial Role in the Context of Global Climate Change." In Abiotic Stress Response in Plants, 13–26. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2016. http://dx.doi.org/10.1002/9783527694570.ch2.

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Sibon, Ody C. M., and William E. Theurkauf. "Centrosome Regulation in Response to Environmental and Genotoxic Stress." In Centrosomes in Development and Disease, 211–23. Weinheim, FRG: Wiley-VCH Verlag GmbH & Co. KGaA, 2005. http://dx.doi.org/10.1002/3527603808.ch11.

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Fatima, Uzma, Mohd Farhan Khan, Jamal e Fatima, Uzma Shahab, Saheem Ahmad, and Mohd Aslam Yusuf. "DNA Damage, Response, and Repair in Plants Under Genotoxic Stress." In Stress Signaling in Plants: Genomics and Proteomics Perspective, Volume 2, 151–71. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-42183-4_7.

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Liu, Yusen, Myriam Gorospe, Nikki J. Holbrook, and Carl W. Anderson. "Posttranslational Mechanisms Leading to Mammalian Gene Activation in Response to Genotoxic Stress." In DNA Damage and Repair, 263–98. Totowa, NJ: Humana Press, 1998. http://dx.doi.org/10.1007/978-1-59259-455-9_15.

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Lücke-Huhle, Christine. "Review: Gene Amplification—A Cellular Response to Genotoxic Stress." In Induced Effects of Genotoxic Agents in Eukaryotic Cells, 81–96. CRC Press, 2020. http://dx.doi.org/10.1201/9781003075387-6.

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Holbrook, Nikki J., Jennifer D. Leuthy, Jong Sung Park, and Joseph Fargnoli. "gadd153, a Growth Arrest and DNA Damage Inducible Gene: Expression in Response to Genotoxic Stress." In Induced Effects of Genotoxic Agents in Eukaryotic Cells, 125–40. CRC Press, 2020. http://dx.doi.org/10.1201/9781003075387-9.

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Pietrucha, Barbara. "Ataxia Telangiectasia." In Ataxia - Practice Essentials and Interventions [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.112005.

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Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar degeneration, telangiectasias, immunodeficiency, recurrent sinopulmonary infections, cancer susceptibility, and radiation sensitivity. AT is a complex disorder, whose neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities: immunoglobulin and antibody deficiencies and lymphopenia. AT patients have an increased predisposition for cancers, particularly of lymphoid origin. AT is caused by mutations in the ataxia telangiectasia mutated (ATM) gene, and the role of the ATM protein is the coordination of cellular signaling pathways in response to DNA double-strand breaks, oxidative stress, and other genotoxic stresses. The diagnosis of AT is usually supported by the combination of neurological clinical features and specific laboratory abnormalities (immunoglobulin A (IgA) deficiency, lymphopenia, and increased alpha-fetoprotein (AFP) levels). There are several other neurological and rare disorders that physicians must consider when diagnosing AT. Treatment of neurological symptoms in patients with AT is only symptomatic and supportive, as there are no known treatments that can slow or stop neurodegeneration. However, other symptoms of AT, such as antibody deficiency, lung disease, developmental disorders, diabetes, or cancer, can be effectively treated. Some hope is associated with the treatment of dexamethasone in the patient’s own blood cells, which relieves neurological symptoms.
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Kondratov, Roman V., Victoria Y. Gorbacheva, and Marina P. Antoch. "The Role of Mammalian Circadian Proteins in Normal Physiology and Genotoxic Stress Responses." In Current Topics in Developmental Biology, 173–216. Elsevier, 2007. http://dx.doi.org/10.1016/s0070-2153(06)78005-x.

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Conference papers on the topic "Genotoxic stress response"

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Nickens, Kristen P., Ying Han, Harini Shandilya, Gary F. Gerard, Eric P. Kaldjian, Jakob Wikstrom, Orian Shirihai, Steven Patierno, and Susan Ceryak. "Abstract 122: Mitochondrial dysregulation and cellular death resistance in response to genotoxic stress." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-122.

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Tessari, Anna, Kareesma Parbhoo, Meghan Pawlikowski, Matteo Fassan, Eliana Rulli, Claudia Foray, Alessandra Fabbri, et al. "Abstract A112: RanBP9 protects cells from genotoxic stress and increased expression is predictive of worse response to platinum in NSCLC patients." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; October 26-30, 2017; Philadelphia, PA. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1535-7163.targ-17-a112.

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Mao, Pingping, Mary Jardine, Lynn Niemaszyk, Jessica Haghkerdar, Eric Yang, Esty G. yanco, Damayanti Desai, et al. "Abstract 2958: The novel protein kinase STK17A is a direct p53 target gene that mediates response to genotoxic and nutritional stress in a cancer cell context-dependent manner." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-2958.

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