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https://www.readbyqxmd.com/read/28230750/targeting%C3%A2-mdm4%C3%A2-splicing%C3%A2-in%C3%A2-cancers
#1
REVIEW
Boris Bardot, Franck Toledo
MDM4, an essential negative regulator of the P53 tumor suppressor, is frequently overexpressed in cancer cells that harbor a wild-type P53. By a mechanism based on alternative splicing, the MDM4 gene generates two mutually exclusive isoforms: MDM4-FL, which encodes the full-length MDM4 protein, and a shorter splice variant called MDM4-S. Previous results suggested that the MDM4-S isoform could be an important driver of tumor development. In this short review, we discuss a recent set of data indicating that MDM4-S is more likely a passenger isoform during tumorigenesis and that targeting MDM4 splicing to prevent MDM4-FL protein expression appears as a promising strategy to reactivate p53 in cancer cells...
February 20, 2017: Genes
https://www.readbyqxmd.com/read/28230739/mnt%C3%A2-and%C3%A2-emerging%C3%A2-concepts%C3%A2-of%C3%A2-mnt-myc-antagonism
#2
Guang Yang, Peter J Hurlin
MYC family proteins play fundamental roles in stem and progenitor cell homeostasis, morphogenesis and cancer. As expected for proteins that profoundly affect the fate of cells, the activities of MYC are regulated at a multitude of levels. One mechanism with the potential to broadly affect the activities of MYC is transcriptional antagonism by a group of MYC-related transcriptional repressors. From this group, the protein MNT has emerged as having perhaps the most far-reaching impact on MYC activities. In this review, we discuss the current understanding of MNT, its regulation and how, as a MYC antagonist, it functions both as a tumor suppressor and facilitator of MYC-driven proliferation and oncogenesis...
February 20, 2017: Genes
https://www.readbyqxmd.com/read/28230735/new-evidence-for-the-theory-of-chromosome-organization-by-repetitive-elements-core
#3
Shao-Jun Tang
Repetitive DNA elements were proposed to coordinate chromatin folding and interaction in chromosomes by their intrinsic homology-based clustering ability. A recent analysis of the data sets from chromosome-conformation-capture experiments confirms the spatial clustering of DNA repeats of the same family in the nuclear space, and thus provides strong new support for the CORE theory.
February 20, 2017: Genes
https://www.readbyqxmd.com/read/28230734/deep%C3%A2-transcriptome%C3%A2-sequencing%C3%A2-of%C3%A2-two%C3%A2-green%C3%A2-algae-chara%C3%A2-vulgaris%C3%A2-and%C3%A2-chlamydomonas%C3%A2-reinhardtii-%C3%A2-provides%C3%A2-no%C3%A2-evidence%C3%A2-of%C3%A2-organellar%C3%A2-rna%C3%A2-editing
#4
A Bruce Cahoon, John A Nauss, Conner D Stanley, Ali Qureshi
Nearly all land plants post-transcriptionally modify specific nucleotides within RNAs, a process known as RNA editing. This adaptation allows the correction of deleterious mutations within the asexually reproducing and presumably non-recombinant chloroplast and mitochondrial genomes. There are no reports of RNA editing in any of the green algae so this phenomenon is presumed to have originated in embryophytes either after the invasion of land or in the now extinct algal ancestor of all land plants. This was challenged when a recent in silico screen for RNA edit sites based on genomic sequence homology predicted edit sites in the green alga Chara vulgaris, a multicellular alga found within the Streptophyta clade and one of the closest extant algal relatives of land plants...
February 20, 2017: Genes
https://www.readbyqxmd.com/read/28218713/transgene-expression-and-host-cell-responses-to-replication-defective-single-cycle-and-replication-competent-adenovirus-vectors
#5
Catherine M Crosby, Michael A Barry
Most adenovirus (Ad) vectors are E1 gene deleted replication defective (RD-Ad) vectors that deliver one transgene to the cell and all expression is based on that one gene. In contrast, E1-intact replication-competent Ad (RC-Ad) vectors replicate their DNA and their transgenes up to 10,000-fold, amplifying transgene expression markedly higher than RD-Ad vectors. While RC-Ad are more potent, they run the real risk of causing adenovirus infections in vector recipients and those that administer them. To gain the benefits of transgene amplification, but avoid the risk of Ad infections, we developed "single cycle" Ad (SC-Ad) vectors...
February 18, 2017: Genes
https://www.readbyqxmd.com/read/28218692/early-insights-from-commercialization-of-gene-therapies-in-europe
#6
Nicolas Touchot, Mathias Flume
After years of research and development, gene therapies are now becoming a commercial reality with several products approved by European regulatory authorities [...].
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28218682/immune-mediated-therapies-for-liver-cancer
#7
REVIEW
Rajagopal N Aravalli, Clifford J Steer
In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28218681/the-intra-s-checkpoint-responses-to-dna-damage
#8
REVIEW
Divya Ramalingam Iyer, Nicholas Rhind
Faithful duplication of the genome is a challenge because DNA is susceptible to damage by a number of intrinsic and extrinsic genotoxins, such as free radicals and UV light. Cells activate the intra-S checkpoint in response to damage during S phase to protect genomic integrity and ensure replication fidelity. The checkpoint prevents genomic instability mainly by regulating origin firing, fork progression, and transcription of G1/S genes in response to DNA damage. Several studies hint that regulation of forks is perhaps the most critical function of the intra-S checkpoint...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28218679/mcm10-a-dynamic-scaffold-at-eukaryotic-replication-forks
#9
REVIEW
Ryan M Baxley, Anja-Katrin Bielinsky
To complete the duplication of large genomes efficiently, mechanisms have evolved that coordinate DNA unwinding with DNA synthesis and provide quality control measures prior to cell division. Minichromosome maintenance protein 10 (Mcm10) is a conserved component of the eukaryotic replisome that contributes to this process in multiple ways. Mcm10 promotes the initiation of DNA replication through direct interactions with the cell division cycle 45 (Cdc45)-minichromosome maintenance complex proteins 2-7 (Mcm2-7)-go-ichi-ni-san GINS complex proteins, as well as single- and double-stranded DNA...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28218666/the-ageing-brain-effects-on-dna-repair-and-dna-methylation-in-mice
#10
Sabine A S Langie, Kerry M Cameron, Gabriella Ficz, David Oxley, Bartłomiej Tomaszewski, Joanna P Gorniak, Lou M Maas, Roger W L Godschalk, Frederik J van Schooten, Wolf Reik, Thomas von Zglinicki, John C Mathers
Base excision repair (BER) may become less effective with ageing resulting in accumulation of DNA lesions, genome instability and altered gene expression that contribute to age-related degenerative diseases. The brain is particularly vulnerable to the accumulation of DNA lesions; hence, proper functioning of DNA repair mechanisms is important for neuronal survival. Although the mechanism of age-related decline in DNA repair capacity is unknown, growing evidence suggests that epigenetic events (e.g., DNA methylation) contribute to the ageing process and may be functionally important through the regulation of the expression of DNA repair genes...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28218662/microrna-expression-profile-identifies-high-grade-non-muscle-invasive-bladder-tumors-at-elevated-risk-to-progress-to-an-invasive-phenotype
#11
Sara M Lenherr, Sheaumei Tsai, Brasil Silva Neto, Travis B Sullivan, Cara B Cimmino, Tanya Logvinenko, Jason Gee, Wei Huang, John A Libertino, Ian C Summerhayes, Kimberly M Rieger-Christ
The objective of this study was to identify a panel of microRNAs (miRNAs) differentially expressed in high-grade non-muscle invasive (NMI; TaG3-T1G3) urothelial carcinoma that progress to muscle-invasive disease compared to those that remain non-muscle invasive, whether recurrence happens or not. Eighty-nine high-grade NMI urothelial carcinoma lesions were identified and total RNA was extracted from paraffin-embedded tissue. Patients were categorized as either having a non-muscle invasive lesion with no evidence of progression over a 3-year period or as having a similar lesion showing progression to muscle invasion over the same period...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28212332/type-1-diabetes-candidate-genes-linked-to-pancreatic-islet-cell-inflammation-and-beta-cell-apoptosis
#12
REVIEW
Joachim Størling, Flemming Pociot
Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28212321/therapeutic-approaches-targeting-myc-driven-prostate-cancer
#13
REVIEW
Richard J Rebello, Richard B Pearson, Ross D Hannan, Luc Furic
The transcript encoding the proto-oncogene MYC is commonly overexpressed in prostate cancer (PC). MYC protein abundance is also increased in the majority of cases of advanced and metastatic castrate-resistant PC (mCRPC). Accordingly, the MYC-directed transcriptional program directly contributes to PC by upregulating the expression of a number of pro-tumorigenic factors involved in cell growth and proliferation. A key cellular process downstream of MYC activity is the regulation of ribosome biogenesis which sustains tumor growth...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28208661/differential-binding-of-three-major-human-adar-isoforms-to-coding-and-long-non-coding-transcripts
#14
Josephine Galipon, Rintaro Ishii, Yutaka Suzuki, Masaru Tomita, Kumiko Ui-Tei
RNA editing by deamination of adenosine to inosine is an evolutionarily conserved process involved in many cellular pathways, from alternative splicing to miRNA targeting. In humans, it is carried out by no less than three major adenosine deaminases acting on RNA (ADARs): ADAR1-p150, ADAR1-p110, and ADAR2. However, the first two derive from alternative splicing, so that it is currently impossible to delete ADAR1-p110 without also knocking out ADAR1-p150 expression. Furthermore, the expression levels of ADARs varies wildly among cell types, and no study has systematically explored the effect of each of these isoforms on the cell transcriptome...
February 11, 2017: Genes
https://www.readbyqxmd.com/read/28208657/fto-genotype-and-type-2-diabetes-mellitus-spatial-analysis-and-meta-analysis-of-62-case-control-studies-from-different-regions
#15
Ying Yang, Boyang Liu, Wei Xia, Jing Yan, Huan-Yu Liu, Ling Hu, Song-Mei Liu
Type 2 diabetes mellitus (T2DM) is a global health problem that results from the interaction of environmental factors with genetic variants. Although a number of studies have suggested that genetic polymorphisms in the fat mass and obesity-associated (FTO) gene are associated with T2DM risk, the results have been inconsistent. To investigate whether FTO polymorphisms associate with T2DM risk and whether this association is region-related, we performed this spatial analysis and meta-analysis. More than 60,000 T2DM patients and 90,000 controls from 62 case-control studies were included in this study...
February 11, 2017: Genes
https://www.readbyqxmd.com/read/28208656/primetime-for-learning-genes
#16
REVIEW
Joyce Keifer
Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells...
February 11, 2017: Genes
https://www.readbyqxmd.com/read/28208635/advances-in-non-viral-dna-vectors-for-gene-therapy
#17
Cinnamon L Hardee, Lirio Milenka Arévalo-Soliz, Benjamin D Hornstein, Lynn Zechiedrich
Uses of viral vectors have thus far eclipsed uses of non-viral vectors for gene therapy delivery in the clinic. Viral vectors, however, have certain issues involving genome integration, the inability to be delivered repeatedly, and possible host rejection. Fortunately, development of non-viral DNA vectors has progressed steadily, especially in plasmid vector length reduction, now allowing these tools to fill in specifically where viral or other non-viral vectors may not be the best options. In this review, we examine the improvements made to non-viral DNA gene therapy vectors, highlight opportunities for their further development, address therapeutic needs for which their use is the logical choice, and discuss their future expansion into the clinic...
February 10, 2017: Genes
https://www.readbyqxmd.com/read/28208626/2-o-methyl-rna-ethylene-bridged-nucleic-acid-chimera-antisense-oligonucleotides-to-induce-dystrophin-exon-45-skipping
#18
REVIEW
Tomoko Lee, Hiroyuki Awano, Mariko Yagi, Masaaki Matsumoto, Nobuaki Watanabe, Ryoya Goda, Makoto Koizumi, Yasuhiro Takeshima, Masafumi Matsuo
Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease characterized by dystrophin deficiency from mutations in the dystrophin gene. Antisense oligonucleotide (AO)-mediated exon skipping targets restoration of the dystrophin reading frame to allow production of an internally deleted dystrophin protein with functional benefit for DMD patients who have out-of-frame deletions. After accelerated US approval of eteplirsen (Exondys 51), which targets dystrophin exon 51 for skipping, efforts are now focused on targeting other exons...
February 10, 2017: Genes
https://www.readbyqxmd.com/read/28208785/dynamics%C3%A2-of%C3%A2-p53-%C3%A2-a%C3%A2-master%C3%A2-decider%C3%A2-of%C3%A2-cell%C3%A2-fate
#19
REVIEW
Qingyin Luo, Jill M Beaver, Yuan Liu, Zunzhen Zhang
Cellular stress-induced temporal alterations-i.e., dynamics-are typically exemplified  by the dynamics of p53 that serve as a master to determine cell fate. p53 dynamics were initially  identified as the variations of p53 protein levels. However, a growing number of studies have  shown that p53 dynamics are also manifested in variations in the activity, spatial location, and  posttranslational modifications of p53 proteins, as well as the interplay among all p53 dynamical  features...
February 9, 2017: Genes
https://www.readbyqxmd.com/read/28208743/elaborated-action-of-the-human-primosome
#20
REVIEW
Andrey G Baranovskiy, Tahir H Tahirov
The human primosome is a 340-kilodalton complex of primase (DNA-dependent RNA polymerase) and DNA polymerase α, which initiates genome replication by synthesizing chimeric RNA-DNA primers for DNA polymerases δ and ϵ. Accumulated biochemical and structural data reveal the complex mechanism of concerted primer synthesis by two catalytic centers. First, primase generates an RNA primer through three steps: initiation, consisting of dinucleotide synthesis from two nucleotide triphosphates; elongation, resulting in dinucleotide extension; and termination, owing to primase inhibition by a mature 9-mer primer...
February 8, 2017: Genes
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