AIMS Genetics最新文献

{"title":"DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity.","authors":"Fabrizio Gentile,&nbsp;Alessia Arcaro,&nbsp;Stefania Pizzimenti,&nbsp;Martina Daga,&nbsp;Giovanni Paolo Cetrangolo,&nbsp;Chiara Dianzani,&nbsp;Alessio Lepore,&nbsp;Maria Graf,&nbsp;Paul R J Ames,&nbsp;Giuseppina Barrera","doi":"10.3934/genet.2017.2.103","DOIUrl":"https://doi.org/10.3934/genet.2017.2.103","url":null,"abstract":"<p><p>Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of some epigenetic factors in DNA damage response pathway","authors":"Mrinalini Tiwari, S. Parvez, P. Agrawala","doi":"10.3934/genet.2017.1.69","DOIUrl":"https://doi.org/10.3934/genet.2017.1.69","url":null,"abstract":"Abstract The current review gives a brief account of the DNA damage response pathway and involvement of various epigenetic mechanisms in DNA damage response pathway. The main focus is on histone modifications leading to structural alterations in chromatin since the compact chromatin structure poses a major limitation in the DNA repair process. Based on this hypothesis, our laboratory has also evaluated certain histone deacetylase inhibitors as potential radiomitigators and the same has been discussed in brief at the end of the review.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45678477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic analysis of DNA damage induction and DNA repair pathway activation by continuous wave visible light laser micro-irradiation","authors":"B. Muster, A. Rapp, M. C. Cardoso","doi":"10.3934/genet.2017.1.47","DOIUrl":"https://doi.org/10.3934/genet.2017.1.47","url":null,"abstract":"Abstract Laser micro-irradiation can be used to induce DNA damage with high spatial and temporal resolution, representing a powerful tool to analyze DNA repair in vivo in the context of chromatin. However, most lasers induce a mixture of DNA damage leading to the activation of multiple DNA repair pathways and making it impossible to study individual repair processes. Hence, we aimed to establish and validate micro-irradiation conditions together with inhibition of several key proteins to discriminate different types of DNA damage and repair pathways using lasers commonly available in confocal microscopes. Using time-lapse analysis of cells expressing fluorescently tagged repair proteins and also validation of the DNA damage generated by micro-irradiation using several key damage markers, we show that irradiation with a 405 nm continuous wave laser lead to the activation of all repair pathways even in the absence of exogenous sensitization. In contrast, we found that irradiation with 488 nm laser lead to the selective activation of non-processive short-patch base excision and single strand break repair, which were further validated by PARP inhibition and metoxyamine treatment. We conclude that these low energy conditions discriminated against processive long-patch base excision repair, nucleotide excision repair as well as double strand break repair pathways.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43096887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A search for the common ground between Tic; Obsessive-compulsive and Autism Spectrum Disorders: part I, Tic disorders","authors":"J. Barnhill, J. Bedford, J. Crowley, T. Soda","doi":"10.3934/genet.2017.1.32","DOIUrl":"https://doi.org/10.3934/genet.2017.1.32","url":null,"abstract":"Abstract This article is the first of four articles designed to explore the complex interrelationship between Autism Spectrum Disorders (ASD); Obsessive compulsive and Related Disorders (OCRD) and Tic Disorders/Tourette's Syndrome (TD/TS). We begin with an overview TD/TS and follow-up with reviews of OCRD and ASD. The final article in this series represents a synthesis of the neurobiological and genetic markers shared by patients presenting with all three syndromes. The goal is to describe the complex endophenotype of these patients in an effort to better define gene markers that underlie these heterogeneous clinical syndromes. Tic disorders (TD) are a collection of hyperkinetic movements that begin in early childhood. Tics are transient for most affected preschool children but a subgroup development persistent movements or progress to develop Tourette Syndrome (TS). TDs as a group display high heritability rates but definitive gene markers still elude us. The difficulty defining genetic markers is in large part due to the diverse neurodevelopmental trajectory, changing topography and typology, development of a broad spectrum of neurocognitive and behavioral complications, and a mixed pattern of psychiatric comorbidities.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46752452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Both <i>RAD5</i>-dependent and independent pathways are involved in DNA damage-associated sister chromatid exchange in budding yeast.","authors":"Michael T Fasullo,&nbsp;Mingzeng Sun","doi":"10.3934/genet.2017.2.84","DOIUrl":"https://doi.org/10.3934/genet.2017.2.84","url":null,"abstract":"<p><p>Sister chromatids are preferred substrates for recombinational repair after cells are exposed to DNA damage. While some agents directly cause double-strand breaks (DSBs), others form DNA base adducts which stall or impede the DNA replication fork. We asked which types of DNA damage can stimulate SCE in budding yeast mutants defective in template switch mechanisms and whether PCNA polyubiquitination functions are required for DNA damage-associated SCE after exposure to potent recombinagens. We measured spontaneous and DNA damage-associated unequal sister chromatid exchange (uSCE) in yeast strains containing two fragments of <i>his3</i> after exposure to MMS, 4-NQO, UV, X rays, and HO endonuclease-induced DSBs. We determined whether other genes in the pathway for template switching, including <i>UBC13</i>, <i>MMS2</i>, <i>SGS1</i>, and <i>SRS2</i> were required for DNA damage-associated SCE. <i>RAD5</i> was required for DNA damage-associated SCE after exposure to UV, MMS, and 4-NQO, but not for spontaneous, X-ray-associated, or HO endonuclease-induced SCE. While <i>UBC13</i>, <i>MMS2</i>, and <i>SGS1</i> were required for MMS and 4NQO-associated SCE, they were not required for UV-associated SCE. DNA damage-associated recombination between <i>his3</i> recombination substrates on non-homologous recombination was enhanced in <i>rad5</i> mutants. These results demonstrate that DNA damaging agents that cause DSBs stimulate SCE by <i>RAD5</i>-independent mechanisms, while several potent agents that generate bulky DNA adducts stimulate SCE by multiple <i>RAD5</i>-dependent mechanisms. We suggest that DSB-associated recombination that occurs in G2 is <i>RAD5</i>-independent.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35075214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unfolding of core nucleosomes by PARP-1 revealed by spFRET microscopy.","authors":"Daniel C Sultanov,&nbsp;Nadezhda S Gerasimova,&nbsp;Kseniya S Kudryashova,&nbsp;Natalya V Maluchenko,&nbsp;Elena Y Kotova,&nbsp;Marie-France Langelier,&nbsp;John M Pascal,&nbsp;Mikhail P Kirpichnikov,&nbsp;Alexey V Feofanov,&nbsp;Vasily M Studitsky","doi":"10.3934/genet.2017.1.21","DOIUrl":"https://doi.org/10.3934/genet.2017.1.21","url":null,"abstract":"<p><p>DNA accessibility to various protein complexes is essential for various processes in the cell and is affected by nucleosome structure and dynamics. Protein factor PARP-1 (poly(ADP-ribose)polymerase 1) increases the accessibility of DNA in chromatin to repair proteins and transcriptional machinery, but the mechanism and extent of this chromatin reorganization are unknown. Here we report on the effects of PARP-1 on single nucleosomes revealed by spFRET (single-particle Förster Resonance Energy Transfer) microscopy. PARP-1 binding to a double-strand break in the vicinity of a nucleosome results in a significant increase of the distance between the adjacent gyres of nucleosomal DNA. This partial uncoiling of the entire nucleosomal DNA occurs without apparent loss of histones and is reversed after poly(ADP)-ribosylation of PARP-1. Thus PARP-1-nucleosome interactions result in reversible, partial uncoiling of the entire nucleosomal DNA.</p>","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35320046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac biomarkers in dialysis","authors":"U. Mahmood, David W. Johnson, M. Fahim","doi":"10.3934/genet.2017.1.1","DOIUrl":"https://doi.org/10.3934/genet.2017.1.1","url":null,"abstract":"Abstract Cardiovascular disease is the major cause of death, accounting for approximately 40 percent of all-cause mortality in patients receiving either hemodialysis or peritoneal dialysis. Cardiovascular risk stratification is an important aspect of managing dialysis patients as it enables early identification of high-risk patients, so therapeutic interventions can be optimized to lower cardiovascular morbidity and mortality. Biomarkers can detect early stages of cardiac injury so timely intervention can be provided. The B-type natriuretic peptides (Brain Natriuretic peptide [BNP] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) and troponins have been shown to predict mortality in dialysis patients. Suppression of tumorigenicity 2 (ST2) and galectin-3 are new emerging biomarkers in the field of heart failure in both the general and dialysis populations. This article aims to discuss the current evidence regarding cardiac biomarker use to diagnose myocardial injury and monitor the risk of major adverse cardiovascular events in patients undergoing dialysis.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody glycosylation as a potential biomarker for chronic inflammatory autoimmune diseases","authors":"J. Knopf, Mona H. C. Biermann, L. Munoz, M. Herrmann","doi":"10.3934/genet.2016.4.280","DOIUrl":"https://doi.org/10.3934/genet.2016.4.280","url":null,"abstract":"Abstract Glycosylation of immunoglobulins (Ig) is known to influence their effector functions in physiological and pathological conditions. Changes in the glycosylation pattern of immunoglobulin G and autoantibodies in various inflammatory autoimmune diseases have been studied for many years. However, despite extensive research, many questions are still elusive regarding the formation of such differentially glycosylated antibodies and alterations of glycosylation patterns in other immunoglobulin classes for example. Nevertheless, knowledge has been deepened greatly, especially in the field of rheumatoid arthritis. Changes of Ig glycosylation patterns have been shown to appear before onset of the disease and moreover can subject to treatment. In this review, we discuss the potential of detecting Ig glycosylation changes as biomarkers for disease activity or monitoring of patients with chronic inflammatory autoimmune diseases such as antiphospholipid syndrome, rheumatoid arthritis, systemic lupus erythematosus, ANCA-associated vasculitis and Henoch-Schönlein purpura.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulation in Autism spectrum disorder","authors":"S. Chaudhury","doi":"10.3934/genet.2016.4.292","DOIUrl":"https://doi.org/10.3934/genet.2016.4.292","url":null,"abstract":"Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by an impaired social communication skill and often results in repetitive, stereotyped behavior which is observed in children during the first few years of life. Other characteristic of this disorder includes language disabilities, difficulties in sensory integration, lack of reciprocal interactions and in some cases, cognitive delays. One percentage of the general population is affected by ASD and is four times more common in boys than girls. There are hundreds of genes, which has been identified to be associated with ASD etiology. However it remains difficult to comprehend our understanding in defining the genetic architecture necessary for complete exposition of its pathophysiology. Seeing the complexity of the disease, it is important to adopt a multidisciplinary approach which should not only focus on the “genetics” of autism but also on epigenetics, transcriptomics, immune system disruption and environmental factors that could all impact the pathogenesis of the disease. As environmental factors also play a key role in regulating the trigger of ASD, the role of chromatin remodeling and DNA methylation has started to emerge. Such epigenetic modifications directly link molecular regulatory pathways and environmental factors, which might be able to explain some aspects of complex disorders like ASD. The present review will focus on the role of epigenetic regulation in defining the underlying cause for ASD.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleosome dynamics: HMGB1 facilitates nucleosome restructuring and collaborates in estrogen-responsive gene expression","authors":"W. Scovell","doi":"10.3934/genet.2016.4.252","DOIUrl":"https://doi.org/10.3934/genet.2016.4.252","url":null,"abstract":"Abstract The genome in the human cell is extraordinarily compacted in the nucleus. As a result, much of the DNA is inaccessible and functionally inert. Notwithstanding the highly efficient packaging, mechanisms have evolved to render DNA sites accessible that then enable a multitude of factors to carry out ongoing and vital functions. The compaction is derived from DNA complexation within nucleosomes, which can further consolidate into a higher-order chromatin structure. The nucleosome and nucleosomal DNA are not static in nature, but are dynamic, undergoing structural and functional changes as the cell responds to stresses and/or metabolic or environmental cues. We are only beginning to understand the forces and the complexes that engage the nucleosome to unearth the tightly bound and inaccessible DNA sequences and provide an opening to more accessible target sites. In many cases, current findings support a major role for the action of ATP-dependent chromatin remodeling complexes (CRCs) in providing an avenue to factor accessibility that leads to the activation of transcription. The estrogen receptor α (ERα) does not bind to the estrogen response element (ERE) in the canonical nucleosome. However, evidence will be presented that HMGB1 restructures the nucleosome in an ATP-independent manner and also facilitates access and strong binding of ERα to ERE. The features that appear important in the mechanism of action for HMGB1 will be highlighted, in addition to the characteristic features of the restructured nucleosome. These findings, together with previous evidence, suggest a collaborative role for HMGB1 in the step-wise transcription of estrogen-responsive genes. In addition, alternate mechanistic pathways will be discussed, with consideration that “HMGB1 restructuring” of the nucleosome may generally be viewed as a perturbation of the equilibrium of an ensemble of nearly isoenergetic nucleosome states in an energy landscape that is driven by conformational selection by HMGB1.","PeriodicalId":43477,"journal":{"name":"AIMS Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70248750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}