scholarly journals The Enigmatic Function of PARP1: From PARylation Activity to PAR Readers

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1625 ◽  
Author(s):  
Tatiana Kamaletdinova ◽  
Zahra Fanaei-Kahrani ◽  
Zhao-Qi Wang
Keyword(s):  
Chromatin Remodeling ◽  
Functional Relationship ◽  
Biological Function ◽  
Future Research ◽  
Cellular Processes ◽  
Founding Member ◽  
Damage Response ◽  
New Research ◽  
Relationship Of ◽  
Research Avenue

Poly(ADP-ribosyl)ation (PARylation) is catalysed by poly(ADP-ribose) polymerases (PARPs, also known as ARTDs) and then rapidly removed by degrading enzymes. Poly(ADP-ribose) (PAR) is produced from PARylation and provides a delicate and spatiotemporal interaction scaffold for numerous target proteins. The PARylation system, consisting of PAR synthesizers and erasers and PAR itself and readers, plays diverse roles in the DNA damage response (DDR), DNA repair, transcription, replication, chromatin remodeling, metabolism, and cell death. Despite great efforts by scientists in biochemistry, cell and molecular biology, genetics, and pharmacology over the last five decades, the biology of PARPs and PARylation remains enigmatic. In this review, we summarize the current understanding of the biological function of PARP1 (ARTD1), the founding member of the PARP family, focusing on the inter-dependent or -independent nature of different functional domains of the PARP1 protein. We also discuss the readers of PAR, whose function may transduce signals and coordinate the cellular processes, which has recently emerged as a new research avenue for PARP biology. We aim to provide some perspective on how future research might disentangle the biology of PARylation by dissecting the structural and functional relationship of PARP1, a major effector of the PARPs family.

scholarly journals SIRT7: a sentinel of genome stability

Open Biology ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 210047
Author(s):  
Ming Tang ◽  
Huangqi Tang ◽  
Bo Tu ◽  
Wei-Guo Zhu
Keyword(s):  
Dna Damage ◽  
Genome Stability ◽  
Biological Function ◽  
Critical Role ◽  
Class Iii ◽  
Cellular Processes ◽  
The Past ◽  
Damage Response ◽  
Normal Gene

SIRT7 is a class III histone deacetylase that belongs to the sirtuin family. The past two decades have seen numerous breakthroughs in terms of understanding SIRT7 biological function. We now know that this enzyme is involved in diverse cellular processes, ranging from gene regulation to genome stability, ageing and tumorigenesis. Genomic instability is one hallmark of cancer and ageing; it occurs as a result of excessive DNA damage. To counteract such instability, cells have evolved a sophisticated regulated DNA damage response mechanism that restores normal gene function. SIRT7 seems to have a critical role in this response, and it is recruited to sites of DNA damage where it recruits downstream repair factors and directs chromatin regulation. In this review, we provide an overview of the role of SIRT7 in DNA repair and maintaining genome stability. We pay particular attention to the implications of SIRT7 function in cancer and ageing.

scholarly journals The PARP Way to Epigenetic Changes

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 446
Author(s):  
Simone Ummarino ◽  
Clinton Hausman ◽  
Annalisa Di Ruscio
Keyword(s):  
Gene Expression ◽  
Chromatin Remodeling ◽  
Dna Damage Response ◽  
Nicotinamide Adenine Dinucleotide ◽  
Epigenetic Changes ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Therapeutic Implications ◽  
Cellular Processes ◽  
Damage Response

ADP-ribosylation, is a reversible post-translational modification implicated in major biological functions. Poly ADP-ribose polymerases (PARP) are specialized enzymes that catalyze the addition of ADP ribose units from “nicotinamide adenine dinucleotide-donor molecules” to their target substrates. This reaction known as PARylation modulates essential cellular processes including DNA damage response, chromatin remodeling, DNA methylation and gene expression. Herein, we discuss emerging roles of PARP1 in chromatin remodeling and epigenetic regulation, focusing on its therapeutic implications for cancer treatment and beyond.

scholarly journals Loss of ATRX sensitizes HeLa cells in response to ionizing irradiation in a manner dependent on the ATM/Chk2 pathway

2020 ◽  
Author(s):  
Geng Tang ◽  
Yanming Yang ◽  
Yuxin Liu ◽  
Bing Han ◽  
Weiqiang Xu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Chromatin Remodeling ◽  
Biological Function ◽  
Ataxia Telangiectasia Mutated ◽  
Ionizing Irradiation ◽  
Alpha Thalassemia ◽  
Downstream Effectors ◽  
Alternative Lengthening ◽  
Damage Response ◽  
Novel Target

Abstract Identifying novel targets for molecular radiosensitization is critical to improve the efficacy of cancer radiotherapy. Alpha-thalassemia/mental retardation X-linked (ATRX), a member of the SWI/SNF-like chromatin remodeling protein family, functions in the maintenance of genomic integrity, alternative lengthening of telomeres, and the regulation of apoptosis and senescence. However, whether ATRX is directly involved in the DNA damage response (DDR) remains unknown. Here, we show that silencing ATRX increased the sensitivity of cells to ionizing radiation (IR). IR-induced DNA damage was greater and G2/M arrest was less efficient in ATRX knockdown cells. ATRX downregulation caused defects in apoptosis and senescence, indicating that ATRX has a biological function in the DDR. ATRX loss led to failure to trigger ataxia telangiectasia-mutated (ATM) auto-phosphorylation, inhibiting the activation of ATM/Chk2 downstream effectors. These data identify ATRX as a novel target for radiosensitization, and its effect depends on inhibition of the ATM/Chk2 pathway in the DDR.

Self-Compassion and Quality of Life in Adults Who Stutter

2020 ◽  
Vol 29 (4) ◽  
pp. 2097-2108
Author(s):  
Robyn L. Croft ◽  
Courtney T. Byrd
Keyword(s):  
Quality Of Life ◽  
Social Connectedness ◽  
The Self ◽  
Future Research ◽  
Self Compassion ◽  
Adults Who Stutter ◽  
And Gender ◽  
Relationship Of ◽  
The Impact

Purpose The purpose of this study was to identify levels of self-compassion in adults who do and do not stutter and to determine whether self-compassion predicts the impact of stuttering on quality of life in adults who stutter. Method Participants included 140 adults who do and do not stutter matched for age and gender. All participants completed the Self-Compassion Scale. Adults who stutter also completed the Overall Assessment of the Speaker's Experience of Stuttering. Data were analyzed for self-compassion differences between and within adults who do and do not stutter and to predict self-compassion on quality of life in adults who stutter. Results Adults who do and do not stutter exhibited no significant differences in total self-compassion, regardless of participant gender. A simple linear regression of the total self-compassion score and total Overall Assessment of the Speaker's Experience of Stuttering score showed a significant, negative linear relationship of self-compassion predicting the impact of stuttering on quality of life. Conclusions Data suggest that higher levels of self-kindness, mindfulness, and social connectedness (i.e., self-compassion) are related to reduced negative reactions to stuttering, an increased participation in daily communication situations, and an improved overall quality of life. Future research should replicate current findings and identify moderators of the self-compassion–quality of life relationship.

Functional Relationship of Polymerization Sites of Vertebrate Fibrinogens

1979 ◽  
Author(s):  
C Cierniewski ◽  
T Krajewski ◽  
E Janiak
Keyword(s):  
Gel Electrophoresis ◽  
Functional Relationship ◽  
Polyacrylamide Gel Electrophoresis ◽  
Polyacrylamide Gel ◽  
Functional Similarity ◽  
Fractionation Method ◽  
Relationship Of ◽  
Fibrin Monomers ◽  
Fibrinogen Molecule ◽  
Cold Ethanol Fractionation

Various studies on the interaction of immobilized mammalian fibrinogen and fibrin monomers with some fibrinogen derivatives demonstrated the presence of two sets of polymerization sites in the mammalian fibrinogen molecule. We obtained the same results while investigating the fibrinogen molecules of other classes of vertebrates /Pisces. Amphibia. Aves/. Despite significant differences among their subunit structures, all of them contain polymerization sites homologous to mammalian counterparts. Moreover, due to great functional similarity, fibrinogen or fibrin monomers of the analyzed species of Pisces. Amphibia. Aves and Mammalia interacted in a specific way with immobilized pig fibrin monomers or fibrinogen, respectively. Using these pig affinity adsorbents, fibrinogen and fibrin monomers of different vertebrates were isolated directly from plasma and analyzed by SDS polyacrylamide gel electrophoresis. Polypeptide compositions of eluted proteins were identical to those obtained for corresponding fibrinogen preparations isolated by cold-ethanol fractionation method. It appears to indicate that the nature of polymerization sites in vertebrate fibrinogens is alike.

The Zoning System for Strategy Development of SMEs Go Online: A Literature Review

2018 ◽  
Author(s):  
Sumitro Sarkum
Keyword(s):  
Development Strategy ◽  
Online Marketing ◽  
Strategy Development ◽  
Future Research ◽  
Information And Communication ◽  
Qualitative Descriptive ◽  
The Government ◽  
Market Needs ◽  
Marketing Information ◽  
Relationship Of

This study aims to figure out what the relationship of empowerment of SMEs through methods of zoning as marketing strategy of SMEs in two different markets (offline and online). The zoning strategy with information and communication system integrated brings together socialization and promotion in a market. This system can help the government in taking and formulating policies to unite SMEs in a new market by not leaving the old market. The method in this study uses qualitative descriptive. There are three propositions produced in this initial research, the first; Offline and online marketing is very relevant for SMEs in Indonesia. Second; marketing information system is access for SMEs to find out the demand or market needs both domestically and internationally. And third; The zoning system can be used as an online development strategy for SMEs to synchronize two different markets, namely offline and online. Further research is needed to validate the propositions found, to generate hypotheses and empirical evidence, we recommend using mix methods for future research.

scholarly journals Evidence for an evolutionary relationship between Vmp1 and bacterial DedA proteins

2019 ◽  
Vol 63 (1-2) ◽  
pp. 67-71 ◽  
Author(s):  
Luis-Carlos Tábara ◽  
Olivier Vincent ◽  
Ricardo Escalante
Keyword(s):  
Experimental Approach ◽  
Functional Relationship ◽  
Evolutionary Relationship ◽  
Transmembrane Proteins ◽  
Lipid Homeostasis ◽  
Molecular Function ◽  
Yeast Protein ◽  
Glycine Residue ◽  
Cellular Processes ◽  
Domain Of Unknown Function

VMP1 and DedA proteins are conserved families of transmembrane proteins in eukaryotes and prokaryotes respectively. Despite numerous reports involving these proteins in multiple cellular processes, their molecular function is still unknown. They share the domain of unknown function PF09335, suggesting a possible functional relationship between these protein families. Here we show that VMP1 from different species contain two short motifs conserved in the bacterial DedA proteins and the yeast protein Tvp38. The hallmark of one of these motifs is a glycine residue previously shown to be strictly conserved in all the DedA proteins. Substitution of this residue to leucine, glutamate or arginine in Dictyostelium Vmp1 inactivates the protein, as shown by the inability of the mutants to rescue the phenotypes associated with the lack of Vmp1 including development and lipid homeostasis. This is the first experimental approach that supports an evolutionary relationship between Vmp1 and DedA proteins and highlights the importance of the conserved glycine residue in the PF09335 domain.

scholarly journals A Generalized Approach for Evaluating the Mechanical Properties of Polymer Nanocomposites Reinforced with Spherical Fillers

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 830
Author(s):  
Julio Cesar Martinez-Garcia ◽  
Alexandre Serraïma-Ferrer ◽  
Aitor Lopeandía-Fernández ◽  
Marco Lattuada ◽  
Janak Sapkota ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Polymeric Nanocomposites ◽  
Mechanical Reinforcement ◽  
Future Studies ◽  
Three Phase ◽  
Theoretical Predictions ◽  
Filler Network ◽  
New Research ◽  
Good Agreement ◽  
Research Avenue

In this work, the effective mechanical reinforcement of polymeric nanocomposites containing spherical particle fillers is predicted based on a generalized analytical three-phase-series-parallel model, considering the concepts of percolation and the interfacial glassy region. While the concept of percolation is solely taken as a contribution of the filler-network, we herein show that the glassy interphase between filler and matrix, which is often in the nanometers range, is also to be considered while interpreting enhanced mechanical properties of particulate filled polymeric nanocomposites. To demonstrate the relevance of the proposed generalized equation, we have fitted several experimental results which show a good agreement with theoretical predictions. Thus, the approach presented here can be valuable to elucidate new possible conceptual routes for the creation of new materials with fundamental technological applications and can open a new research avenue for future studies.

scholarly journals Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Diseases ◽  
3D Models ◽  
Model Systems ◽  
Spinocerebellar Ataxias ◽  
C Elegans ◽  
Cellular Processes ◽  
Age Related ◽  
Damage Response ◽  
Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

scholarly journals Co-Creating New Directions for Service Robots in Hospitality and Tourism

2021 ◽  
Vol 2 (1) ◽  
pp. 43-61
Author(s):  
Francesc Fusté-Forné ◽  
Tazim Jamal
Keyword(s):  
Ethical Issues ◽  
Research Literature ◽  
Service Robots ◽  
Future Research ◽  
Research Attention ◽  
Research And Practice ◽  
Tourism Management ◽  
New Directions ◽  
Hospitality And Tourism ◽  
New Research

Research on the relationship between automation services and tourism has been rapidly growing in recent years and has led to a new service landscape where the role of robots is gaining both practical and research attention. This paper builds on previous reviews and undertakes a comprehensive analysis of the research literature to discuss opportunities and challenges presented by the use of service robots in hospitality and tourism. Management and ethical issues are identified and it is noted that practical and ethical issues (roboethics) continue to lack attention. Going forward, new directions are urgently needed to inform future research and practice. Legal and ethical issues must be proactively addressed, and new research paradigms developed to explore the posthumanist and transhumanist transitions that await. In addition, closer attention to the potential of “co-creation” for addressing innovations in enhanced service experiences in hospitality and tourism is merited. Among others, responsibility, inclusiveness and collaborative human-robot design and implementation emerge as important principles to guide future research and practice in this area.

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