Construction of DNA damage response genepprI function-deficient and function-complementary mutants inDeinococcus radiodurans

2005 ◽  
Vol 50 (4) ◽  
pp. 311-316 ◽  
Author(s):  
Guanjun Gao ◽  
Huiming Lu ◽  
Lifen Huang ◽  
Yuejin Hua
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Damage Response ◽  
And Function

scholarly journals PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response

2021 ◽  
Author(s):  
Rodolfo Bortolozo Serafim ◽  
Cibele Cardoso ◽  
Vanessa Arfelli ◽  
Valeria Valente ◽  
Leticia Fröhlich Archangelo
Keyword(s):  
Dna Damage ◽  
Nervous System ◽  
Dna Damage Response ◽  
Cellular Proliferation ◽  
Patient Survival ◽  
Glioblastoma Cells ◽  
Damage Response ◽  
Genotoxic Agents ◽  
And Migration ◽  
And Function

Abstract PIMREG expression strongly correlates with cellular proliferation in both malignant and normal cells. Throughout embryo development, PIMREG expression is prominent at the central nervous system. Recent studies have described high levels of PIMREG transcripts in different types of tumors and correlated with patient survival and tumor aggressiveness. Given the emerging significance of PIMREG in carcinogenesis and its putative role in the context of the nervous system, we investigated the expression and function of PIMREG in gliomas, the most common primary brain tumors. We performed an extensive analysis of PIMREG expression in tumors samples of glioma patients, assessed the effects of PIMREG silencing and overexpression on the sensitivity of glioblastoma cell lines treated with genotoxic agents commonly used for treating patients and assessed for treatment response, proliferation and migration. We show that glioblastoma exhibits the highest levels of PIMREG expression among all cancers analyzed and that elevated PIMREG expression is a biomarker for glioma progression and patient outcome. Moreover, PIMREG is induced by genotoxic agents and its silencing renders glioblastoma cells sensitive to temozolomide treatment and affects ATR- and ATM-dependent signaling. Our data demonstrate that PIMREG plays a role in DNA damage response and temozolomide resistance of glioblastoma cells and further support the PIMREG role in tumorigenesis.

scholarly journals Ubiquitylation, neddylation and the DNA damage response

Open Biology ◽  
2015 ◽  
Vol 5 (4) ◽  
pp. 150018 ◽  
Author(s):  
Jessica S. Brown ◽  
Stephen P. Jackson
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Cellular Response ◽  
Dna Double Strand Breaks ◽  
Post Translational Modification ◽  
Strand Breaks ◽  
Damage Sensing ◽  
Damage Response ◽  
Repair Mechanisms ◽  
And Function

Failure of accurate DNA damage sensing and repair mechanisms manifests as a variety of human diseases, including neurodegenerative disorders, immunodeficiency, infertility and cancer. The accuracy and efficiency of DNA damage detection and repair, collectively termed the DNA damage response (DDR), requires the recruitment and subsequent post-translational modification (PTM) of a complex network of proteins. Ubiquitin and the ubiquitin-like protein (UBL) SUMO have established roles in regulating the cellular response to DNA double-strand breaks (DSBs). A role for other UBLs, such as NEDD8, is also now emerging. This article provides an overview of the DDR, discusses our current understanding of the process and function of PTM by ubiquitin and NEDD8, and reviews the literature surrounding the role of ubiquitylation and neddylation in DNA repair processes, focusing particularly on DNA DSB repair.

Viral Infection Sentinel Rig-I Maintains Hematopoietic Stem Cell Function Through Regulating DNA-Damage Response

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1166-1166
Author(s):  
Wu Zhang ◽  
Meng-Lei Ding ◽  
Xian-Yang Li ◽  
He-Zhou Guo ◽  
Hong-Xin Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Cell Function ◽  
Conflicts Of Interest ◽  
Dna Lesions ◽  
Type I ◽  
Hematopoietic Stem ◽  
Damage Response ◽  
Underlying Mechanisms ◽  
And Function

Abstract Throughout life hematopoietic stem cells (HSCs) have to cope with various kinds of insults from inflammation to DNA damage constantly to maintain the integrity of stemness. It is possible that certain core factors are commonly implicated in the maintenance of HSC pool and function under discrete physiological and pathological conditions. However, the underlying mechanisms remain largely unexplored. Previous works have demonstrated that retinoic acid inducible gene I (Rig-I) plays an essential role in recognizing viral RNA and activating type I IFN transcription, but whether Rig-I is involved in the core program governing HSCs’ behaviors is unclear. Here, we report that in the steady status Rig-I deficiency significantly increased HSC number by dysregulating the cell-cycling status of HSCs in mice. However, HSCs in Rig-I-/- mice were actually more sensitive to genotoxic treatments such as irradiation as compared to wild type HSCs, causing more Rig-I-/- mice to die of hematopoietic exhaustion. In accordance, HSC transplantation assays showed a significant impact of Rig-I loss on the hematopoietic regeneration capacity. Mechanistically, we found that Rig-I represented a pivotal component of the molecular pathways that mediate DNA-damage response and the repair of DNA lesions. Taken together, these data indicate a crucial role of innate immunity-regulatory factor Rig-I in the maintenance of HSCs. Disclosures: No relevant conflicts of interest to declare.

Phosphorylation of FANCA on S1449 Is Important for Fanconi Anemia (FA) Pathway Function.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 186-186
Author(s):  
Natalie B. Collins ◽  
Andrei Tomashevski ◽  
Gary M. Kupfer
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Dna Damage Response ◽  
Fanconi Anemia ◽  
Phosphorylation Site ◽  
Site Directed Mutagenesis ◽  
Wild Type ◽  
Damage Response ◽  
And Function ◽  
Mutant Cells

Abstract Previous work in our lab and others has shown that the Fanconi anemia proteins, FANCG and FANCA, are phosphoproteins. FANCG is phosphorylated at mitosis, and these phosphorylations are required for proper exit from chromatin at mitosis. FANCG is also phosphorylated after DNA damage, with the phosphorylation site required for wild-type sensitivity to DNA damaging agents. FANCA is also phosphorylated after DNA damage and localized to chromatin, but the site and significance of this phosphorylation were previously unknown. Mass spectrometry of FANCA revealed one phosphopeptide with phosphorylation on serine 1449. Site-directed mutagenesis of this residue to alanine (S1449A) abolished a slower mobility form of FANCA seen after MMC treatment. Furthermore, the S1449A mutant failed to completely correct the MMC hypersensitivity of FA-A mutant cells. S1449A mutant cells displayed lower than wild-type levels of FANCD2 monoubiquitination following DNA damage, and an increased number of gross chromosomal aberrations were seen in metaphase spreads from S1449A mutant cells when compared to wild type cells. Using a GFP reporter substrate to measure homologous recombination, cells expressing the S1449A FANCA failed to completely correct the homologous recombination defect seen in FA cells. Taken together, cells expressing FANCA S1449A display a variety of FA-associated phenotypes, suggesting that the phosphorylation of S1449 is a functionally significant event. The DNA damage response in human cells is, in large part, coordinated by phosphorylation events initiated by apical kinases ATM and ATR. S1449 is found in a consensus ATM site, therefore studies are underway to determine if ATM or ATR is the kinase responsible for FANCA phosphorylation at S1449. Phosphorylation is a crucial process in transducing the DNA damage response, and phosphorylation of FA proteins appears critical to both localization and function of the proteins. Understanding how phosphorylation marks are placed on FANCA will give insight into the role of FANCA in the DNA damage response.

scholarly journals Preserving genome integrity and function: the DNA damage response and histone modifications

2019 ◽  
Vol 54 (3) ◽  
pp. 208-241 ◽  
Author(s):  
Jae Jin Kim ◽  
Seo Yun Lee ◽  
Kyle M. Miller
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Histone Modifications ◽  
Genome Integrity ◽  
Damage Response ◽  
And Function

scholarly journals Post-translational Modifications of Fumarase Regulate its Enzyme Activity and Function in Respiration and the DNA Damage Response

2020 ◽  
Vol 432 (23) ◽  
pp. 6108-6126
Author(s):  
Suqing Wang ◽  
Dharanidharan Ramamurthy ◽  
Jasper Tan ◽  
Jingyan Liu ◽  
Joyce Yip ◽  
...  
Keyword(s):  
Dna Damage ◽  
Enzyme Activity ◽  
Dna Damage Response ◽  
Post Translational Modifications ◽  
Damage Response ◽  
And Function

scholarly journals Multifunctionality of the Telomere-Capping Shelterin Complex Explained by Variations in Its Protein Composition

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1753
Author(s):  
Claire Ghilain ◽  
Eric Gilson ◽  
Marie-Josèphe Giraud-Panis
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Replicative Senescence ◽  
Protein Composition ◽  
Functional Independence ◽  
Shelterin Complex ◽  
Damage Response ◽  
Telomere Capping ◽  
Development And Aging ◽  
And Function

Protecting telomere from the DNA damage response is essential to avoid the entry into cellular senescence and organismal aging. The progressive telomere DNA shortening in dividing somatic cells, programmed during development, leads to critically short telomeres that trigger replicative senescence and thereby contribute to aging. In several organisms, including mammals, telomeres are protected by a protein complex named Shelterin that counteract at various levels the DNA damage response at chromosome ends through the specific function of each of its subunits. The changes in Shelterin structure and function during development and aging is thus an intense area of research. Here, we review our knowledge on the existence of several Shelterin subcomplexes and the functional independence between them. This leads us to discuss the possibility that the multifunctionality of the Shelterin complex is determined by the formation of different subcomplexes whose composition may change during aging.

scholarly journals RASSF Signalling and DNA Damage: Monitoring the Integrity of the Genome?

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Simon F. Scrace ◽  
Eric O'Neill
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Cancer Therapies ◽  
Oncogenic Pathways ◽  
Damage Response ◽  
Damage Monitoring ◽  
Dna Damage Signalling ◽  
And Function ◽  
The Guardian

The RASSF family of proteins has been extensively studied in terms of their genetics, structure and function. One of the functions that has been increasingly studied is the role of the RASSF proteins in the DNA damage response. Surprisingly, this research, which encompasses both the classical and N-terminal RASSF proteins, has revealed an involvement of the RASSFs in oncogenic pathways as well as the more familiar tumour suppressor pathways usually associated with the RASSF family members. The most studied protein with respect to DNA damage is RASSF1A, which has been shown, not only to be activated by ATM, a major regulator of the DNA damage response, but also to bind to and activate a number of different pathways which all lead to and feedback from the guardian of the genome, p53. In this review we discuss the latest research linking the RASSF proteins to DNA damage signalling and maintenance of genomic integrity and look at how this knowledge is being utilised in the clinic to enhance the effectiveness of traditional cancer therapies such as radiotherapy.

scholarly journals The Response to DNA Damage at Telomeric Repeats and Its Consequences for Telomere Function

Genes ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 318 ◽  
Author(s):  
Doksani
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Structure And Function ◽  
Telomeric Repeats ◽  
Damage Response ◽  
Telomere Function ◽  
Linear Chromosomes ◽  
And Function ◽  
Key Steps ◽  
Telomere Structure

Telomeric repeats, coated by the shelterin complex, prevent inappropriate activation of the DNA damage response at the ends of linear chromosomes. Shelterin has evolved distinct solutions to protect telomeres from different aspects of the DNA damage response. These solutions include formation of t-loops, which can sequester the chromosome terminus from DNA-end sensors and inhibition of key steps in the DNA damage response. While blocking the DNA damage response at chromosome ends, telomeres make wide use of many of its players to deal with exogenous damage and replication stress. This review focuses on the interplay between the end-protection functions and the response to DNA damage occurring inside the telomeric repeats, as well as on the consequences that telomere damage has on telomere structure and function.

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