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"Genomic integration"

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https://www.readbyqxmd.com/read/29330025/the-role-of-extracellular-and-intracellular-nicotinamide-phosphoribosyl-transferase-in-cancer-diagnostic-and-therapeutic-perspectives-and-challenges
#1
REVIEW
Maria Dalamaga, Gerasimos Socrates Christodoulatos, Christos S Mantzoros
Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties...
January 9, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29326044/escherichia-coli-single-stranded-dna-binding-protein-ssb-promotes-alkb-mediated-dna-dealkylation-repair
#2
Richa Nigam, Roy Anindya
Repair of alkylation damage in DNA is essential for maintaining genome integrity. Escherichia coli (E.coli) protein AlkB removes various alkyl DNA adducts including N1-methyladenine (N1meA) and N3-methylcytosine (N3meC) by oxidative demethylation. Previous studies showed that AlkB preferentially removes N1meA and N3meC from single-stranded DNA (ssDNA). It can also remove N1meA and N3meC from double-stranded DNA by base-flipping. Notably, ssDNA produced during DNA replication and recombination, remains bound to E...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29321305/arabidopsis-rna-polymerase-v-mediates-enhanced-compaction-and-silencing-of-geminivirus-and-transposon-chromatin-during-host-recovery-from-infection
#3
Tami Coursey, Elizabeth Regedanz, David M Bisaro
Plants employ RNA-directed DNA methylation (RdDM) and dimethylation of histone 3 lysine 9 (H3K9me2) to silence geminiviruses and transposable elements (TEs). We previously showed that canonical RdDM (Pol IV-RdDM) involving RNA polymerases IV and V (Pol IV and Pol V) is required for Arabidopsis thaliana to recover from infection with Beet curly top virus lacking a suppressor protein that inhibits methylation (BCTV L2-). Recovery, which is characterized by reduced viral DNA levels and symptom remission, allows normal floral development...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321190/genomic-landscape-of-pancreatic-neuroendocrine-tumours-the-international-cancer-genome-consortium
#4
Andrea Mafficini, Aldo Scarpa
Neuroendocrine tumours (NETs) may arise throughout the body and are a highly heterogeneous, relatively rare class of neoplasms difficult to study also for the lack of disease models. Despite this, knowledge on their molecular alterations has expanded in the latest years, also building from genetic syndromes causing their onset. Pancreatic NETs (PanNETs) have been among the most studied, and research so far has outlined a series of recurring features, as inactivation of MEN1, VHL, TSC1/2 genes, and hyperactivation of the PI3K/mTOR pathway...
January 10, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29304399/establishment-of-induced-pluripotent-stem-cell-line-zzui009-a-from-an-alzheimer-s-disease-patient-carrying-a-psen1-gene-mutation
#5
Yanlin Wang, Na Jing, Linlin Su, Changhe Shi, Pei Zhang, Zhilei Wang, Huifang Sun, Jing Yang, Yutao Liu, Xuejun Wen, Jin Zhang, Shoutao Zhang, Yuming Xu
Skin fibroblasts were obtained from a 42-year-old Alzheimer's disease (AD) patient carrying mutations in the PSEN1 gene. An iPSC line was successfully established using the Sendai-virus (SeV) delivery system. The patient-specific iPSCs were free of genomically integrated reprogramming genes, had the specific mutation, expressed the expected pluripotency markers, and had the potential to differentiate into cells of all three germ layers. Our model might offer a robust platform for further study of the pathomechanism of this disease as well as drug testing and gene therapy studies...
December 12, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29300933/structural-characterization-of-the-asf1-rtt109-interaction-and-its-role-in-histone-acetylation
#6
Lukas Lercher, Nataliya Danilenko, John Kirkpatrick, Teresa Carlomagno
Acetylation of histone H3 at lysine-56 by the histone acetyltransferase Rtt109 in lower eukaryotes is important for maintaining genomic integrity and is required for C. albicans pathogenicity. Rtt109 is activated by association with two different histone chaperones, Vps75 and Asf1, through an unknown mechanism. Here, we reveal that the Rtt109 C-terminus interacts directly with Asf1 and elucidate the structural basis of this interaction. In addition, we find that the H3 N-terminus can interact via the same interface on Asf1, leading to a competition between the two interaction partners...
December 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29290612/removal-of-rtf2-from-stalled-replisomes-promotes-maintenance-of-genome-integrity
#7
Molly C Kottemann, Brooke A Conti, Francis P Lach, Agata Smogorzewska
The protection and efficient restart of stalled replication forks is critical for the maintenance of genome integrity. Here, we identify a regulatory pathway that promotes stalled forks recovery from replication stress. We show that the mammalian replisome component C20orf43/RTF2 (homologous to S. pombe Rtf2) must be removed for fork restart to be optimal. We further show that the proteasomal shuttle proteins DDI1 and DDI2 are required for RTF2 removal from stalled forks. Persistence of RTF2 at stalled forks results in fork restart defects, hyperactivation of the DNA damage signal, accumulation of single-stranded DNA (ssDNA), sensitivity to replication drugs, and chromosome instability...
December 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29286535/the-changing-landscape-of-lynch-syndrome-due-to-pms2-mutations
#8
REVIEW
J Blount, A Prakash
DNA repair pathways are essential for cellular survival as our DNA is constantly under assault from both exogenous and endogenous DNA damaging agents. Five major mammalian DNA repair pathways exist within a cell to maintain genomic integrity. Of these, the DNA mismatch repair (MMR) pathway is highly conserved among species and is well documented in bacteria. In humans, the importance of MMR is underscored by the discovery that a single mutation in any one of four genes within the MMR pathway (MLH1, MSH2, MSH6 and PMS2) results in Lynch syndrome (LS)...
December 29, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/29282689/brca-gene-mutations-and-poly-adp-ribose-polymerase-inhibitors-in-triple-negative-breast-cancer
#9
Hitomi Sumiyoshi Okuma, Kan Yonemori
Breast cancer is the most common cancer in women worldwide. Treatment is chosen according to its hormone receptor status and human epidermal growth factor receptor 2 (HER2) status. Among the four main clinically set subtypes, hormone receptor-negative/HER2-negative subtype, also called triple-negative subtype (TNBC), is the most aggressive type with limited choices of therapy. However, recent research has provided important new insights into effective treatments for this subtype. One molecular target that has gained attention is the BRCA gene...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29282095/impact-of-fhit-loss-on-the-translation-of-cancer-associated-mrnas
#10
Daniel L Kiss, William Baez, Kay Huebner, Ralf Bundschuh, Daniel R Schoenberg
BACKGROUND: FHIT is a genome caretaker/tumor suppressor that is silenced in >50% of cancers. Although it was identified more than 20 years ago, questions remain as to how FHIT loss contributes to cancer, and conversely, how FHIT acts to maintain genome integrity and suppress malignancy. Fhit belongs to the histidine triad family of enzymes that catalyze the degradation of nucleoside 5',5'-triphosphates, including the m7GpppN 'caps' that are generated when mRNAs undergo 3'-5' decay...
December 28, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29281970/transcriptional-effects-of-a-positive-feedback-circuit-in-drosophila-melanogaster
#11
Jarosław Bryk, R Guy Reeves, Floyd A Reed, Jai A Denton
BACKGROUND: Synthetic systems that use positive feedback have been developed to control human disease vectors and crop pests. The tTAV system, which has been deployed in several insect species, relies on a positive feedback circuit that can be inhibited via dietary tetracycline. Although insects carrying tTAV fail to survive until adulthood in the absence of tetracycline, the exact reason for its lethality, as well as the transcriptomic effects of an active positive feedback circuit, remain unknown...
December 28, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29281624/the-smc5-6-complex-regulates-the-yeast-mph1-helicase-at-rna-dna-hybrid-mediated-dna-damage
#12
Juan Lafuente-Barquero, Sarah Luke-Glaser, Marco Graf, Sonia Silva, Belén Gómez-González, Arianna Lockhart, Michael Lisby, Andrés Aguilera, Brian Luke
RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In the absence of RNase H enzymes, RNA-DNA hybrids accumulate, resulting in replication stress, DNA damage and compromised genomic integrity. We demonstrate that Mph1, the yeast homolog of Fanconi anemia protein M (FANCM), is required for cell viability in the absence of RNase H enzymes. The integrity of the Mph1 helicase domain is crucial to prevent the accumulation of RNA-DNA hybrids and RNA-DNA hybrid-dependent DNA damage, as determined by Rad52 foci...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29281264/piwi-interacting-rna-in-drosophila-biogenesis-transposon-regulation-and-beyond
#13
Haruna Yamashiro, Mikiko C Siomi
PIWI-interacting RNAs (piRNAs) are germline-enriched small RNAs that control transposons to maintain genome integrity. To achieve this, upon being processed from piRNA precursors, most of which are transcripts of intergenic piRNA clusters, piRNAs bind PIWI proteins, germline-specific Argonaute proteins, to form effector complexes. The mechanism of this piRNA-mediated transposon silencing pathway is fundamentally similar to that of siRNA/miRNA-dependent gene silencing in that a small RNA guides its partner Argonaute protein to target gene transcripts for repression via RNA-RNA base pairing...
December 27, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/29279302/genetic-evidence-for-roles-of-yeast-mitotic-cyclins-at-single-stranded-gaps-created-by-dna-replication
#14
Laurence Signon
Paused/stalled replication forks are major threats to genome integrity; unraveling the complex pathways that contribute to fork stability/restart is crucial. Experimentally, fork stalling is induced by growth in presence of hydroxyurea (HU), which depletes the pool of deoxynucleoside triphosphates (dNTPs) and slows down replication progression in yeast. Here, I report an epistasis analysis, based on sensitivity to HU, between CLB2, the principal mitotic cyclin gene in S. cerevisiae, and genes involved in fork stability and recombination...
December 26, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29261229/in-vitro-histone-acetylation-assay
#15
James A L Brown
Acetylation is a core cellular process involved in maintaining genomic integrity, gene regulation, and metabolism. Histone acetyltransferases (HATs) are an enzyme family that regulates these processes by catalyzing the transfer of an acetyl moiety onto target proteins. Perturbations of cellular acetylation profiles have been associated with a variety of disease states, including cancer. Changes in acetylation profiles can be achieved by mechanisms associated with acetyltransferases, such as gene down-regulation or alterations in the activity of key acetyltransferase enzymes...
December 20, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/29260452/emerging-roles-of-sirtuin-6-in-alzheimer-s-disease
#16
REVIEW
Nurul Fatihah Mohamad Nasir, Azalina Zainuddin, Shaharum Shamsuddin
Alzheimer's disease (AD) is a neurodegenerative disease that is imposing an increasing burden on society. Currently, AD is the leading cause of senile dementia worldwide. Despite the long existence of AD, there is lack of therapies for AD, suggesting that new and effective treatment strategy must be explored. At present, sirtuin pathway has attracted attention from the researchers due to its promising results in laboratory models of aging. In addition, our understanding in the roles of sirtuin 6 in AD has expanded...
December 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29250096/methylation-sensitive-amplification-polymorphism-sequencing-msap-seq-a-method-for-high-throughput-analysis-of-differentially-methylated-ccgg-sites-in-plants-with-large-genomes
#17
Karolina Chwialkowska, Urszula Korotko, Joanna Kosinska, Iwona Szarejko, Miroslaw Kwasniewski
Epigenetic mechanisms, including histone modifications and DNA methylation, mutually regulate chromatin structure, maintain genome integrity, and affect gene expression and transposon mobility. Variations in DNA methylation within plant populations, as well as methylation in response to internal and external factors, are of increasing interest, especially in the crop research field. Methylation Sensitive Amplification Polymorphism (MSAP) is one of the most commonly used methods for assessing DNA methylation changes in plants...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29246583/dna-structural-basis-for-fragility-at-peak-iii-of-bcl2-major-breakpoint-region-associated-with-t-14-18-translocation
#18
Saniya Javadekar, Rakhee Yadav, Sathees C Raghavan
Maintaining genome integrity is crucial for normal cellular functions. DNA double-strand breaks (DSBs), when unrepaired, can potentiate chromosomal translocations. t(14;18) translocation involving BCL2 gene on chromosome 18 and IgH loci at chromosome 14, could lead to follicular lymphoma. Molecular basis for fragility of translocation breakpoint regions is an active area of investigation. Previously, formation of non-B DNA structures like G-quadruplex, triplex, B/A transition were investigated at peak I of BCL2 major breakpoint region (MBR); however, it is less understood at peak III...
December 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29246570/integration-free-induced-pluripotent-stem-cells-derived-from-a-patient-with-autosomal-recessive-alport-syndrome-aras
#19
Bernd Kuebler, Begoña Aran, Laia Miquel-Serra, Yolanda Muñoz, Elisabet Ars, Gemma Bullich, Monica Furlano, Roser Torra, Merce Marti, Anna Veiga, Angel Raya
A skin biopsy was obtained from a 25-year-old female patient with autosomal recessive Alport syndrome (ARAS) with the homozygous COL4A3 mutation c.345delG, p.(P166Lfs*37). Dermal fibroblasts were derived and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53shRNA. The generated induced Pluripotent Stem Cell (iPSC) clone AS FiPS1 Ep6F-2 was free of genomically integrated reprogramming genes, had the specific homozygous mutation, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro...
December 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29244158/znf830-mediates-cancer-chemoresistance-through-promoting-homologous-recombination-repair
#20
Guo Chen, Jianxiang Chen, Yiting Qiao, Yaru Shi, Wei Liu, Qi Zeng, Hui Xie, Xiaorui Shi, Youwei Sun, Xu Liu, Tongyu Li, Liqian Zhou, Jianqin Wan, Tian Xie, Hangxiang Wang, Fu Wang
Homologous recombination (HR), which mediates the repair of DNA double-strand breaks (DSB), is crucial for maintaining genomic integrity and enhancing survival in response to chemotherapy and radiotherapy in human cancers. However, the mechanisms of HR repair in treatment resistance for the improvement of cancer therapy remains unclear. Here, we report that the zinc finger protein 830 (ZNF830) promotes HR repair and the survival of cancer cells in response to DNA damage. Mechanistically, ZNF830 directly participates in DNA end resection via interacting with CtIP and regulating CtIP recruitment to DNA damage sites...
December 13, 2017: Nucleic Acids Research
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