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"Genomic integration"

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https://www.readbyqxmd.com/read/28087943/rna-interference-in-fungi-retention-and-loss
#1
Francisco E Nicolás, Victoriano Garre
RNA interference (RNAi) is a mechanism conserved in eukaryotes, including fungi, that represses gene expression by means of small noncoding RNAs (sRNAs) of about 20 to 30 nucleotides. Its discovery is one of the most important scientific breakthroughs of the past 20 years, and it has revolutionized our perception of the functioning of the cell. Initially described and characterized in Neurospora crassa, the RNAi is widespread in fungi, suggesting that it plays important functions in the fungal kingdom. Several RNAi-related mechanisms for maintenance of genome integrity, particularly protection against exogenous nucleic acids such as mobile elements, have been described in several fungi, suggesting that this is the main function of RNAi in the fungal kingdom...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087673/rdna-stability-is-supported-by-many-buffer-genes-introduction-to-the-yeast-rdna-stability-database
#2
Takehiko Kobayashi, Mariko Sasaki
The ribosomal RNA gene (rDNA) is the most abundant gene in yeast and other eukaryotic organisms. Due to its heavy transcription, repetitive structure and programmed replication fork pauses, the rDNA is one of the most unstable regions in the genome. Thus, the rDNA is the best region to study the mechanisms responsible for maintaining genome integrity. Recently, we screened a library of ∼4,800 budding yeast gene knockout strains to identify mutants defective in the maintenance of rDNA stability. The results of this screen are summarized in the Yeast rDNA Stability Database, in which the stability and copy number of rDNA in each mutant are presented...
January 12, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28079255/moonlighting-at-replication-forks-a-new-life-for-homologous-recombination-proteins-brca1-brca2-and-rad51
#3
REVIEW
Arun Mouli Kolinjivadi, Vincenzo Sannino, Anna de Antoni, Hervé Técher, Giorgio Baldi, Vincenzo Costanzo
Coordination between DNA replication and DNA repair ensures maintenance of genome integrity, which is lost in cancer cells. Emerging evidence has linked Homologous Recombination (HR) proteins RAD51, BRCA1 and BRCA2 to the stability of nascent DNA. This function appears to be distinct from Double Strand Break (DSB) repair and is in part due to the prevention of MRE11-mediated degradation of nascent DNA at stalled forks. The role of RAD51 in fork protection resembles the activity described for its prokaryotic ortholog RecA, which prevents nuclease-mediated degradation of DNA and promotes replication fork restart in cells challenged by DNA damaging agents...
January 12, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28073246/a-new-era-of-genome-integration-simply-cut-and-paste
#4
Zihe Liu, Youyun Liang, Ee-Lui Ang, Huimin Zhao
Genome integration is a powerful tool in both basic and applied biological research. However, traditional genome integration, which is typically mediated by homologous recombination, has been constrained by low efficiencies and limited host range. In recent years, the emergence of homing endonucleases and programmable nucleases has greatly enhanced integration efficiencies and allowed alternative integration mechanisms such as non-homologous end joining and microhomology-mediated end joining, enabling integration in hosts deficient in homologous recombination...
January 10, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28072566/guard-the-guardian-a-crl4-ligase-stands-watch-over-histone-production
#5
Fabienne Lampert, Mia M L Brodersen, Matthias Peter
Histones are evolutionarily conserved proteins that together with DNA constitute eukaryotic chromatin in a defined stoichiometry. Core histones are dynamic scaffolding proteins that undergo a myriad of post-translational modifications, which selectively engage chromosome condensation, replication, transcription and DNA damage repair. Cullin4-RING ubiquitin E3 ligases are known to hold pivotal roles in a wide spectrum of chromatin biology ranging from chromatin remodeling and transcriptional repression, to sensing of cytotoxic DNA lesions...
January 10, 2017: Nucleus
https://www.readbyqxmd.com/read/28069372/rna-exosome-and-non-coding-rna-coupled-mechanisms-in-aid-mediated-genomic-alterations
#6
REVIEW
Brice Laffleur, Uttiya Basu, Junghyun Lim
The eukaryotic RNA exosome is a well-conserved protein complex with ribonuclease activity implicated in RNA metabolism. Various families of non-coding RNAs have been identified as substrates of the complex, underscoring its role as a non-coding RNA processing/degradation unit. However, the role of RNA exosome and its RNA processing activity on DNA mutagenesis/alteration events have not been investigated until recently. B lymphocytes use two DNA alteration mechanisms, class switch recombination (CSR) and somatic hypermutation (SHM), to re-engineer their antibody gene expressing loci until a tailored antibody gene for a specific antigen is satisfactorily generated...
January 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28068556/organizing-dna-repair-in-the-nucleus-dsbs-hit-the-road
#7
REVIEW
Aline Marnef, Gaëlle Legube
In the past decade, large-scale movements of DNA double strand breaks (DSBs) have repeatedly been identified following DNA damage. These mobility events include clustering, anchoring or peripheral movement at subnuclear structures. Recent work suggests roles for motion in homology search and in break sequestration to preclude deleterious outcomes. Yet, the precise functions of these movements still remain relatively obscure, and the same holds true for the determinants. Here we review recent advances in this exciting area of research, and highlight that a recurrent characteristic of mobile DSBs may lie in their inability to undergo rapid repair...
January 6, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28067915/histone-degradation-in-response-to-dna-damage-enhances-chromatin-dynamics-and-recombination-rates
#8
Michael H Hauer, Andrew Seeber, Vijender Singh, Raphael Thierry, Ragna Sack, Assaf Amitai, Mariya Kryzhanovska, Jan Eglinger, David Holcman, Tom Owen-Hughes, Susan M Gasser
Nucleosomes are essential for proper chromatin organization and the maintenance of genome integrity. Histones are post-translationally modified and often evicted at sites of DNA breaks, facilitating the recruitment of repair factors. Whether such chromatin changes are localized or genome-wide is debated. Here we show that cellular levels of histones drop 20-40% in response to DNA damage. This histone loss occurs from chromatin, is proteasome-mediated and requires both the DNA damage checkpoint and the INO80 nucleosome remodeler...
January 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28067843/maintenance-of-genome-integrity-how-mammalian-cells-orchestrate-genome-duplication-by-coordinating-replicative-and-specialized-dna-polymerases
#9
REVIEW
Ryan Barnes, Kristin Eckert
Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication...
January 6, 2017: Genes
https://www.readbyqxmd.com/read/28062032/direct-visualization-of-helicase-dynamics-using-fluorescence-localization-and-optical-trapping
#10
C-T Lin, T Ha
Helicases control the accessibility of single-stranded (ss) nucleic acid (NA) generated as a transient intermediate during almost every step in cells related to nucleic acid metabolisms. For subsequent processing, however, helicases need to adjust the pace of unwinding adequately to avoid ssNA exposure to nucleases. Therefore, understanding how the unwinding process of helicases is regulated is crucial to address genome integrity and repair mechanisms. Using single-molecule fluorescence-force spectroscopy with fluorescence localization, we recently observed the stoichiometry of UvrD helicase, which determines the functions of UvrD: translocation and unwinding...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28060283/preparation-of-raav9-to-overexpress-or-knockdown-genes-in-mouse-hearts
#11
Jian Ding, Zhi-Qiang Lin, Jian-Ming Jiang, Christine E Seidman, Jonathan G Seidman, William T Pu, Da-Zhi Wang
Controlling the expression or activity of specific genes through the myocardial delivery of genetic materials in murine models permits the investigation of gene functions. Their therapeutic potential in the heart can also be determined. There are limited approaches for in vivo molecular intervention in the mouse heart. Recombinant adeno-associated virus (rAAV)-based genome engineering has been utilized as an essential tool for in vivo cardiac gene manipulation. The specific advantages of this technology include high efficiency, high specificity, low genomic integration rate, minimal immunogenicity, and minimal pathogenicity...
December 17, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28059856/lack-of-correlation-between-x-ray-repair-cross-complementing-group-1-gene-polymorphisms-and-the-susceptibility-to-colorectal-cancer-in-a-malaysian-cohort
#12
Tze-Pheng Lau, Lay-Hoong Lian, Phaik-Leng Cheah, Lai-Meng Looi, April C Roslani, Khean-Lee Goh, Ping-Chin Lee, Kek-Heng Chua
X-ray repair cross-complementing group 1 (XRCC1) is one of the key components in the base excision repair pathway that repairs erroneous DNA lesions and removes nonbulky base adducts for the maintenance of genome integrity. Studies have revealed that differences in individual DNA repair capacity can impact the interindividual variation in cancer susceptibility, tumour aggressiveness and treatment response. The relationship between XRCC1 and sporadic colorectal cancer (CRC) susceptibility, which is hitherto inconclusive, has been explored in many association studies of different populations...
January 4, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28059076/structure-of-the-cohesin-loader-scc2
#13
William C H Chao, Yasuto Murayama, Sofía Muñoz, Andrew W Jones, Benjamin O Wade, Andrew G Purkiss, Xiao-Wen Hu, Aaron Borg, Ambrosius P Snijders, Frank Uhlmann, Martin R Singleton
The functions of cohesin are central to genome integrity, chromosome organization and transcription regulation through its prevention of premature sister-chromatid separation and the formation of DNA loops. The loading of cohesin onto chromatin depends on the Scc2-Scc4 complex; however, little is known about how it stimulates the cohesion-loading activity. Here we determine the large 'hook' structure of Scc2 responsible for catalysing cohesin loading. We identify key Scc2 surfaces that are crucial for cohesin loading in vivo...
January 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28055177/effect-of-genomic-integration-location-on-heterologous-protein-expression-and-metabolic-engineering-in-e-coli
#14
Jacob A Englaender, John Andrew Jones, Brady F Cress, Thomas E Kuhlman, Robert J Linhardt, Mattheos A G Koffas
Chromosomal integration offers a selection-free alternative to DNA plasmids for expression of foreign proteins and metabolic pathways. Episomal plasmid DNA is convenient but has drawbacks including increased metabolic burden and the requirement for selection in the form of antibiotics. E. coli has long been used for the expression of foreign proteins and for the production of valuable metabolites by expression of complete metabolic pathways. The gene encoding the fluorescent reporter protein mCherry was integrated into four genomic loci on the E...
January 5, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28049757/smug2-dna-glycosylase-from-pedobacter-heparinus-as-a-new-subfamily-in-udg-superfamily
#15
Panjiao Pang, Ye Yang, Jing Li, Zhong Wang, Weiguo Cao, Wei Xie
Base deamination is a common type of DNA damage that occurs in all organisms. DNA repair mechanisms are essential to maintain genome integrity, in which the base excision repair (BER) pathway plays a major role in the removal of base damage. In the BER pathway, the uracil DNA glycosylase superfamily is responsible for excising the deaminated bases from DNA and generates apurinic/apyrimidinic (AP) sites. Using bioinformatics tools, we identified a family 3 SMUG1-like DNA glycoyslase from Pedobacter heparinus (named as Phe SMUG2), which display catalytic activities towards DNA containing uracil or hypoxanthine/xanthine...
January 3, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28049704/the-nucleotide-excision-repair-pathway-limits-l1-retrotransposition
#16
Geraldine Servant, Vincent A Streva, Rebecca S Derbes, Madushani I Wijetunge, Marc Neeland, Travis B White, Victoria P Belancio, Astrid M Roy-Engel, Prescott L Deininger
Long interspersed elements 1 (L1) are active mobile elements that constitute almost 17% of the human genome. They amplify through a "copy-and-paste" mechanism termed retrotransposition, and de novo insertions related to these elements have been reported to cause 0.2% of genetic diseases. Our previous data demonstrated that the endonuclease complex ERCC1-XPF, which cleaves a 3' DNA flap structure, limits L1 retrotransposition. Although the ERCC1-XPF endonuclease participates in several different DNA repair pathways, such as single-strand annealing, or in telomere maintenance, its recruitment to DNA lesions is best characterized in the nucleotide excision repair (NER) pathway...
January 2017: Genetics
https://www.readbyqxmd.com/read/28049654/histone-lysine-demethylase-inhibitors
#17
REVIEW
Ashwini Jambhekar, Jamie N Anastas, Yang Shi
The dynamic regulation of covalent modifications to histones is essential for maintaining genomic integrity and cell identity and is often compromised in cancer. Aberrant expression of histone lysine demethylases has been documented in many types of blood and solid tumors, and thus demethylases represent promising therapeutic targets. Recent advances in high-throughput chemical screening, structure-based drug design, and structure-activity relationship studies have improved both the specificity and the in vivo efficacy of demethylase inhibitors...
January 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28040742/a-role-for-the-twins-protein-phosphatase-pp2a-b55-in-the-maintenance-of-drosophila-genome-integrity
#18
Chiara Merigliano, Antonio Marzio, Fioranna Renda, Maria Patrizia Somma, Maurizio Gatti, Fiammetta Vernì
The protein phosphatase 2A (PP2A) is a conserved heterotrimeric enzyme that regulates several cellular processes including the DNA damage response and mitosis. Consistent with these functions, PP2A is mutated in many types of cancer and acts as a tumor suppressor. In mammalian cells, PP2A inhibition results in DNA double strand breaks (DSBs) and chromosome aberrations (CABs). However, the mechanisms through which PP2A prevents DNA damage are still unclear. Here, we focus on the role of the Drosophila twins (tws) gene in the maintenance of chromosome integrity; tws encodes the B regulatory subunit (B/B55) of PP2A...
December 30, 2016: Genetics
https://www.readbyqxmd.com/read/28040729/polycomb-repressive-complex-1-provides-a-molecular-explanation-for-repeat-copy-number-dependency-in-fshd-muscular-dystrophy
#19
Valentina Casa, Valeria Runfola, Stefano Micheloni, Arif Aziz, F Jeffrey Dilworth, Davide Gabellini
Repression of repetitive elements is crucial to preserve genome integrity and has been traditionally ascribed to constitutive heterochromatin pathways. FacioScapuloHumeral Muscular Dystrophy (FSHD), one of the most common myopathies, is characterized by a complex interplay of genetic and epigenetic events. The main FSHD form is linked to reduced copy number of the D4Z4 macrosatellite repeat on 4q35, causing loss of silencing and aberrant expression of the D4Z4-embedded DUX4 gene leading to disease. By an unknown mechanism, D4Z4 copy-number correlates with FSHD phenotype...
December 30, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28039910/bk-polyomavirus-genomic-integration-and-large-t-antigen-expression-evolving-paradigms-in-human-oncogenesis
#20
Daniel J Kenan, Piotr A Mieczkowski, Eva Latulippe, Isabelle Côté, Harsharan K Singh, Volker Nickeleit
Human polyomaviruses are ubiquitous, with primary infections typically occurring during childhood and subsequent latency that may last a lifetime. Polyomavirus-mediated disease has been described in immunocompromised patients; its relationship to oncogenesis is poorly understood. Here we present deep sequencing data from a high grade BK virus-associated tumor expressing large T antigen. The carcinoma arose in a kidney allograft six years after transplantation. We identified a novel genotype-1a BK polyomavirus (termed "Chapel Hill BK polyomavirus-2″) that was integrated into the BRE gene in chromosome 2 of tumor cells...
December 31, 2016: American Journal of Transplantation
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