scholarly journals The interplay between DNA damage response and RNA processing: the unexpected role of splicing factors as gatekeepers of genome stability

2015 ◽  
Vol 6 ◽  
Author(s):  
Chiara Naro ◽  
Pamela Bielli ◽  
Vittoria Pagliarini ◽  
Claudio Sette
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Rna Processing ◽  
Genome Stability ◽  
Splicing Factors ◽  
Damage Response

Maintenance of genome stability: the unifying role of interconnections between the DNA damage response and RNA-processing pathways

2018 ◽  
Vol 64 (5) ◽  
pp. 971-983 ◽  
Author(s):  
B. Mikolaskova ◽  
M. Jurcik ◽  
I. Cipakova ◽  
M. Kretova ◽  
M. Chovanec ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Rna Processing ◽  
Genome Stability ◽  
Damage Response ◽  
Processing Pathways

scholarly journals Multifunctional Role of ATM/Tel1 Kinase in Genome Stability: From the DNA Damage Response to Telomere Maintenance

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Enea Gino Di Domenico ◽  
Elena Romano ◽  
Paola Del Porto ◽  
Fiorentina Ascenzioni
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Genome Stability ◽  
Genetic Disorder ◽  
Cell Cycle Control ◽  
Premature Aging ◽  
Telomere Maintenance ◽  
Damage Response

The mammalian protein kinase ataxia telangiectasia mutated (ATM) is a key regulator of the DNA double-strand-break response and belongs to the evolutionary conserved phosphatidylinositol-3-kinase-related protein kinases. ATM deficiency causes ataxia telangiectasia (AT), a genetic disorder that is characterized by premature aging, cerebellar neuropathy, immunodeficiency, and predisposition to cancer. AT cells show defects in the DNA damage-response pathway, cell-cycle control, and telomere maintenance and length regulation. Likewise, inSaccharomyces cerevisiae, haploid strains defective in theTEL1gene, the ATM ortholog, show chromosomal aberrations and short telomeres. In this review, we outline the complex role of ATM/Tel1 in maintaining genomic stability through its control of numerous aspects of cellular survival. In particular, we describe how ATM/Tel1 participates in the signal transduction pathways elicited by DNA damage and in telomere homeostasis and its importance as a barrier to cancer development.

scholarly journals RNA Splicing: A New Player in the DNA Damage Response

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Silvia C. Lenzken ◽  
Alessia Loffreda ◽  
Silvia M. L. Barabino
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Rna Splicing ◽  
Genome Stability ◽  
Genetic Alterations ◽  
Splicing Factors ◽  
Hereditary Cancers ◽  
Damage Response ◽  
Multistep Process ◽  
Checkpoint Genes

It is widely accepted that tumorigenesis is a multistep process characterized by the sequential accumulation of genetic alterations. However, the molecular basis of genomic instability in cancer is still partially understood. The observation that hereditary cancers are often characterized by mutations in DNA repair and checkpoint genes suggests that accumulation of DNA damage is a major contributor to the oncogenic transformation. It is therefore of great interest to identify all the cellular pathways that contribute to the response to DNA damage. Recently, RNA processing has emerged as a novel pathway that may contribute to the maintenance of genome stability. In this review, we illustrate several different mechanisms through which pre-mRNA splicing and genomic stability can influence each other. We specifically focus on the role of splicing factors in the DNA damage response and describe how, in turn, activation of the DDR can influence the activity of splicing factors.

scholarly journals DNA Damage Response in Multiple Myeloma: The Role of the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 504
Author(s):  
Takayuki Saitoh ◽  
Tsukasa Oda
Keyword(s):  
Multiple Myeloma ◽  
Dna Damage ◽  
Dna Repair ◽  
Tumor Microenvironment ◽  
Dna Damage Response ◽  
Genetic Instability ◽  
Dna Repair Mechanisms ◽  
Damage Response ◽  
Repair Mechanisms

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by genomic instability. MM cells present various forms of genetic instability, including chromosomal instability, microsatellite instability, and base-pair alterations, as well as changes in chromosome number. The tumor microenvironment and an abnormal DNA repair function affect genetic instability in this disease. In addition, states of the tumor microenvironment itself, such as inflammation and hypoxia, influence the DNA damage response, which includes DNA repair mechanisms, cell cycle checkpoints, and apoptotic pathways. Unrepaired DNA damage in tumor cells has been shown to exacerbate genomic instability and aberrant features that enable MM progression and drug resistance. This review provides an overview of the DNA repair pathways, with a special focus on their function in MM, and discusses the role of the tumor microenvironment in governing DNA repair mechanisms.

Dissecting the Role of Thyrotropin in the DNA Damage Response in Human Thyrocytes after 131I, γ Radiation and H2O2

2019 ◽  
Vol 105 (3) ◽  
pp. 839-853
Author(s):  
Aglaia Kyrilli ◽  
David Gacquer ◽  
Vincent Detours ◽  
Anne Lefort ◽  
Frédéric Libert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Iodide Uptake ◽  
Transcriptomic Response ◽  
Uptake Inhibition ◽  
Γ Radiation ◽  
Damage Response

Abstract Background The early molecular events in human thyrocytes after 131I exposure have not yet been unravelled. Therefore, we investigated the role of TSH in the 131I-induced DNA damage response and gene expression in primary cultured human thyrocytes. Methods Following exposure of thyrocytes, in the presence or absence of TSH, to 131I (β radiation), γ radiation (3 Gy), and hydrogen peroxide (H2O2), we assessed DNA damage, proliferation, and cell-cycle status. We conducted RNA sequencing to profile gene expression after each type of exposure and evaluated the influence of TSH on each transcriptomic response. Results Overall, the thyrocyte responses following exposure to β or γ radiation and to H2O2 were similar. However, TSH increased 131I-induced DNA damage, an effect partially diminished after iodide uptake inhibition. Specifically, TSH increased the number of DNA double-strand breaks in nonexposed thyrocytes and thus predisposed them to greater damage following 131I exposure. This effect most likely occurred via Gα q cascade and a rise in intracellular reactive oxygen species (ROS) levels. β and γ radiation prolonged thyroid cell-cycle arrest to a similar extent without sign of apoptosis. The gene expression profiles of thyrocytes exposed to β/γ radiation or H2O2 were overlapping. Modulations in genes involved in inflammatory response, apoptosis, and proliferation were observed. TSH increased the number and intensity of modulation of differentially expressed genes after 131I exposure. Conclusions TSH specifically increased 131I-induced DNA damage probably via a rise in ROS levels and produced a more prominent transcriptomic response after exposure to 131I.

Role of H2AX in DNA damage response and human cancers

2009 ◽  
Vol 681 (2-3) ◽  
pp. 180-188 ◽  
Author(s):  
Niloo Srivastava ◽  
Sailesh Gochhait ◽  
Peter de Boer ◽  
Rameshwar N.K. Bamezai
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Human Cancers ◽  
Damage Response

scholarly journals A novel role of the chromokinesin Kif4A in DNA damage response

Cell Cycle ◽  
2008 ◽  
Vol 7 (13) ◽  
pp. 2013-2020 ◽  
Author(s):  
Guikai Wu ◽  
Longen Zhou ◽  
Lily Khidr ◽  
Xuning Emily Guo ◽  
Wankee Kim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Damage Response
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