scholarly journals Microtubular and Nuclear Functions of γ-Tubulin: Are They LINCed?

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 259 ◽  
Author(s):  
Jana Chumová ◽  
Hana Kourová ◽  
Lucie Trögelová ◽  
Petr Halada ◽  
Pavla Binarová
Keyword(s):  
Chromatin Remodeling ◽  
Dna Damage Response ◽  
Tumor Suppressors ◽  
Molecular Mechanisms ◽  
Nuclear Organization ◽  
Linc Complex ◽  
Cellular Functions ◽  
Microtubule Nucleation ◽  
Damage Response

γ-Tubulin is a conserved member of the tubulin superfamily with a function in microtubule nucleation. Proteins of γ-tubulin complexes serve as nucleation templates as well as a majority of other proteins contributing to centrosomal and non-centrosomal nucleation, conserved across eukaryotes. There is a growing amount of evidence of γ-tubulin functions besides microtubule nucleation in transcription, DNA damage response, chromatin remodeling, and on its interactions with tumor suppressors. However, the molecular mechanisms are not well understood. Furthermore, interactions with lamin and SUN proteins of the LINC complex suggest the role of γ-tubulin in the coupling of nuclear organization with cytoskeletons. γ-Tubulin that belongs to the clade of eukaryotic tubulins shows characteristics of both prokaryotic and eukaryotic tubulins. Both human and plant γ-tubulins preserve the ability of prokaryotic tubulins to assemble filaments and higher-order fibrillar networks. γ-Tubulin filaments, with bundling and aggregating capacity, are suggested to perform complex scaffolding and sequestration functions. In this review, we discuss a plethora of γ-tubulin molecular interactions and cellular functions, as well as recent advances in understanding the molecular mechanisms behind them.

scholarly journals The Role of E3, E4 Ubiquitin Ligase (UBE4B) in Human Pathologies

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 62 ◽  
Author(s):  
Nikolaos Antoniou ◽  
Nefeli Lagopati ◽  
Dimitrios Ilias Balourdas ◽  
Michail Nikolaou ◽  
Alexandros Papalampros ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Ubiquitin Ligase ◽  
Molecular Mechanisms ◽  
Ubiquitin Ligases ◽  
Cellular Functions ◽  
P53 Expression ◽  
Damage Response ◽  
Mechanisms Of Carcinogenesis

The genome is exposed daily to many deleterious factors. Ubiquitination is a mechanism that regulates several crucial cellular functions, allowing cells to react upon various stimuli in order to preserve their homeostasis. Ubiquitin ligases act as specific regulators and actively participate among others in the DNA damage response (DDR) network. UBE4B is a newly identified member of E3 ubiquitin ligases that appears to be overexpressed in several human neoplasms. The aim of this review is to provide insights into the role of UBE4B ubiquitin ligase in DDR and its association with p53 expression, shedding light particularly on the molecular mechanisms of carcinogenesis.

scholarly journals HERC Ubiquitin Ligases in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1653
Author(s):  
Joan Sala-Gaston ◽  
Arturo Martinez-Martinez ◽  
Leonardo Pedrazza ◽  
L. Francisco Lorenzo-Martín ◽  
Rubén Caloto ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Suppressors ◽  
Molecular Mechanisms ◽  
Ubiquitin Ligases ◽  
Tumor Type ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Damage Response ◽  
Herc Proteins

HERC proteins are ubiquitin E3 ligases of the HECT family. The HERC subfamily is composed of six members classified by size into large (HERC1 and HERC2) and small (HERC3–HERC6). HERC family ubiquitin ligases regulate important cellular processes, such as neurodevelopment, DNA damage response, cell proliferation, cell migration, and immune responses. Accumulating evidence also shows that this family plays critical roles in cancer. In this review, we provide an integrated view of the role of these ligases in cancer, highlighting their bivalent functions as either oncogenes or tumor suppressors, depending on the tumor type. We include a discussion of both the molecular mechanisms involved and the potential therapeutic strategies.

scholarly journals The Emerging Role of Cohesin in the DNA Damage Response

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 581 ◽  
Author(s):  
Ireneusz Litwin ◽  
Ewa Pilarczyk ◽  
Robert Wysocki
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Developmental Disorders ◽  
Molecular Mechanisms ◽  
Genetic Material ◽  
Dna Damage Signaling ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Damage Response

Faithful transmission of genetic material is crucial for all organisms since changes in genetic information may result in genomic instability that causes developmental disorders and cancers. Thus, understanding the mechanisms that preserve genome integrity is of fundamental importance. Cohesin is a multiprotein complex whose canonical function is to hold sister chromatids together from S-phase until the onset of anaphase to ensure the equal division of chromosomes. However, recent research points to a crucial function of cohesin in the DNA damage response (DDR). In this review, we summarize recent advances in the understanding of cohesin function in DNA damage signaling and repair. First, we focus on cohesin architecture and molecular mechanisms that govern sister chromatid cohesion. Next, we briefly characterize the main DDR pathways. Finally, we describe mechanisms that determine cohesin accumulation at DNA damage sites and discuss possible roles of cohesin in DDR.

Role of Tumor Suppressors in DNA Damage Response

2003 ◽  
pp. 39-50
Author(s):  
Bin-Bing S. Zhou ◽  
Michael R. Mattern ◽  
Kum Kum Khanna
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Tumor Suppressors ◽  
Damage Response

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
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