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"Genomic integration"

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https://www.readbyqxmd.com/read/28644387/rna-binding-proteins-and-genome-integrity
#1
REVIEW
Kensei Nishida, Yuki Kuwano, Tatsuya Nishikawa, Kiyoshi Masuda, Kazuhito Rokutan
Genome integrity can be threatened by various endogenous or exogenous events. To counteract these stressors, the DNA damage response network contributes to the prevention and/or repair of genomic DNA damage and serves an essential function in cellular survival. DNA binding proteins are involved in this network. Recently, several RNA-binding proteins (RBPs) that are recruited to DNA damage sites have been shown to be direct players in the prevention or repair of DNA damage. In addition, non-coding RNAs, themselves, are involved in the RNA-mediated DNA repair system...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28642369/replisome-mediated-translesion-synthesis-by-a-cellular-replicase
#2
Philip Nevin, Carolina C Gabbai, Kenneth J Marians
Genome integrity relies on the ability of the replisome to navigate ubiquitous DNA damage during DNA replication. The Escherichia coli replisome transiently stalls at leading-strand template lesions and can either reinitiate replication downstream of the lesion or recruit specialized DNA polymerases that can bypass the lesion via translesion synthesis. Previous results had suggested that the E. coli replicase might play a role in lesion bypass, but this possibility has not been tested in reconstituted DNA replication systems...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28641941/role-of-recombination-and-replication-fork-restart-in-repeat-instability
#3
REVIEW
Erica J Polleys, Nealia C M House, Catherine H Freudenreich
Eukaryotic genomes contain many repetitive DNA sequences that exhibit size instability. Some repeat elements have the added complication of being able to form secondary structures, such as hairpin loops, slipped DNA, triplex DNA or G-quadruplexes. Especially when repeat sequences are long, these DNA structures can form a significant impediment to DNA replication and repair, leading to DNA nicks, gaps, and breaks. In turn, repair or replication fork restart attempts within the repeat DNA can lead to addition or removal of repeat elements, which can sometimes lead to disease...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28640207/reverse-gyrase-functions-in-genome-integrity-maintenance-by-protecting-dna-breaks-in-vivo
#4
Wenyuan Han, Xu Feng, Qunxin She
Reverse gyrase introduces positive supercoils to circular DNA and is implicated in genome stability maintenance in thermophiles. The extremely thermophilic crenarchaeon Sulfolobus encodes two reverse gyrase proteins, TopR1 (topoisomerase reverse gyrase 1) and TopR2, whose functions in thermophilic life remain to be demonstrated. Here, we investigated the roles of TopR1 in genome stability maintenance in S. islandicus in response to the treatment of methyl methanesulfonate (MMS), a DNA alkylation agent. Lethal MMS treatment induced two successive events: massive chromosomal DNA backbone breakage and subsequent DNA degradation...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28636953/dicer-deficiency-differentially-impacts-microglia-of-the-developing-and-adult-brain
#5
Diana Varol, Alexander Mildner, Thomas Blank, Anat Shemer, Neta Barashi, Simon Yona, Eyal David, Sigalit Boura-Halfon, Yifat Segal-Hayoun, Louise Chappell-Maor, Hadas Keren-Shaul, Dena Leshkowitz, Eran Hornstein, Martin Fuhrmann, Ido Amit, Nicola Maggio, Marco Prinz, Steffen Jung
Microglia seed the embryonic neuro-epithelium, expand and actively sculpt neuronal circuits in the developing central nervous system, but eventually adopt relative quiescence and ramified morphology in the adult. Here, we probed the impact of post-transcriptional control by microRNAs (miRNAs) on microglial performance during development and adulthood by generating mice lacking microglial Dicer expression at these distinct stages. Conditional Dicer ablation in adult microglia revealed that miRNAs were required to limit microglial responses to challenge...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28634376/structural-basis-to-stabilize-the-domain-motion-of-bard1-ard-brct-by-cstf50
#6
Rajan Kumar Choudhary, Mohd Quadir Siddiqui, Pankaj S Thapa, Nikhil Gadewal, Senthil Kumar Nachimuthu, Ashok K Varma
BRCA1 associated ring domain protein 1(BARD1) is a tumor suppressor protein having a wide role in cellular processes like cell-cycle checkpoint, DNA damage repair and maintenance of genomic integrity. Germ-line mutation Gln 564 His discovered in linker region of BARD1 leads to loss of binding to Cleavage stimulating factor (CstF50), which in turn instigates the premature mRNA transcript formation and apoptosis. We have studied the dynamics of ARD domain present in the BARD1 wild-type and mutant protein in association with CstF50 using biophysical, biochemical and molecular dynamics simulations...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630472/smyd3-promotes-homologous-recombination-via-regulation-of-h3k4-mediated-gene-expression
#7
Yun-Ju Chen, Cheng-Hui Tsai, Pin-Yu Wang, Shu-Chun Teng
SMYD3 is a methyltransferase highly expressed in many types of cancer. It usually functions as an oncogenic protein to promote cell cycle, cell proliferation, and metastasis. Here, we show that SMYD3 modulates another hallmark of cancer, DNA repair, by stimulating transcription of genes involved in multiple steps of homologous recombination. Deficiency of SMYD3 induces DNA-damage hypersensitivity, decreases levels of repair foci, and leads to impairment of homologous recombination. Moreover, the regulation of homologous recombination-related genes is via the methylation of H3K4 at the target gene promoters...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627256/potential-contributions-of-antioxidants-to-cancer-therapy
#8
Anita Thyagarajan-Sahu, Ravi P Sahu
Antioxidants play important roles in the maintenance of cellular integrity and thus are critical in maintaining the homeostasis of the host immune system. A balance between the levels of pro-oxidants and antioxidants defines the cellular fate of genomic integrity via maintaining the redox status of the cells. An aberration in this balance modulates host immunity that affects normal cellular signaling pathways resulting in uncontrolled proliferation of cells leading to neocarcinogenesis. For decades, there have been scientific debates on the use of antioxidants for the treatment of human cancers...
March 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28624614/gene-transfer-agent-promotes-evolvability-within-the-fittest-subpopulation-of-a-bacterial-pathogen
#9
Maxime Québatte, Matthias Christen, Alexander Harms, Jonas Körner, Beat Christen, Christoph Dehio
The Bartonella gene transfer agent (BaGTA) is an archetypical example for domestication of a phage-derived element to permit high-frequency genetic exchange in bacterial populations. Here we used multiplexed transposon sequencing (TnSeq) and single-cell reporters to globally define the core components and transfer dynamics of BaGTA. Our systems-level analysis has identified inner- and outer-circle components of the BaGTA system, including 55 regulatory components, as well as an additional 74 and 107 components mediating donor transfer and recipient uptake functions...
June 14, 2017: Cell Systems
https://www.readbyqxmd.com/read/28624371/histone-ubiquitination-in-the-dna-damage-response
#10
REVIEW
Michael Uckelmann, Titia K Sixma
DNA double strand breaks need to be repaired in an organized fashion to preserve genomic integrity. In the organization of faithful repair, histone ubiquitination plays a crucial role. Recent findings suggest an integrated model for DNA repair regulation through site-specific histone ubiquitination and crosstalk to other posttranslational modifications. Here we discuss how site-specific histone ubiquitination is achieved on a molecular level and how different multi-protein complexes work together to integrate different histone ubiquitination states...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28623888/ub-isap-a-streamlined-unix-pipeline-for-mining-unique-viral-vector-integration-sites-from-next-generation-sequencing-data
#11
Atul Kamboj, Claus V Hallwirth, Ian E Alexander, Geoffrey B McCowage, Belinda Kramer
BACKGROUND: The analysis of viral vector genomic integration sites is an important component in assessing the safety and efficiency of patient treatment using gene therapy. Alongside this clinical application, integration site identification is a key step in the genetic mapping of viral elements in mutagenesis screens that aim to elucidate gene function. RESULTS: We have developed a UNIX-based vector integration site analysis pipeline (Ub-ISAP) that utilises a UNIX-based workflow for automated integration site identification and annotation of both single and paired-end sequencing reads...
June 17, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28620865/involvement-of-atm-and-trp53-in-neural-cell-loss-due-to-terf2-inactivation-during-mouse-brain-development
#12
Jusik Kim, Inseo Choi, Youngsoo Lee
Maintenance of genomic integrity is one of the critical features for proper neurodevelopment and inhibition of neurological diseases. The signals from both ATM and ATR to TP53 are well-known mechanisms to remove neural cells with DNA damage during neurogenesis. Here we examined the involvement of Atm and Atr in genomic instability due to Terf2 inactivation during mouse brain development. Selective inactivation of Terf2 in neural progenitors induced apoptosis, resulting in a complete loss of the brain structure...
June 15, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28620011/dietary-restriction-but-not-angiotensin-ii-type-1-receptor-blockade-improves-dna-damage-related-vasodilator-dysfunction%C3%A2-in-rapidly-aging-ercc1-%C3%AE-mice
#13
Haiyan Wu, Bibi S van Thiel, Paula Katherine Bautista-Nino, Erwin Reiling, Matej Durik, Frank P J Leijten, Yanto Ridwan, Renata M C Brandt, Harry van Steeg, Martijn E T Dollé, Wilbert P Vermeij, Jan H J Hoeijmakers, Jeroen Essers, Ingrid van der Pluijm, A H Jan Danser, Anton J M Roks
DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model ( Ercc1(∆/-) mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system ...
June 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28615282/maternal-haploid-a-metalloprotease-enriched-at-the-largest-satellite-repeat-and-essential-for-genome-integrity-in-drosophila-embryos
#14
Xiaona Tang, Jingguo Cao, Liang Zhang, Yingzi Huang, Qianyi Zhang, Yikang S Rong
The incorporation of the paternal genome into the zygote during fertilization requires chromatin remodeling. The maternal haploid (mh) mutation in Drosophila affects this process and leads to the formation of haploid embryos without the paternal genome. mh encodes the Drosophila homolog of SPRTN, a conserved protease essential for resolving DNA-protein cross-linked products. Here we characterize the role of MH in genome maintenance. It is not understood how MH protects the paternal genome during fertilization particularly in lights of our finding that MH is present in both parental pro-nuclei during zygote formation...
June 14, 2017: Genetics
https://www.readbyqxmd.com/read/28614305/bap1-regulates-ip3r3-mediated-ca-2-flux-to-mitochondria-suppressing-cell-transformation
#15
Angela Bononi, Carlotta Giorgi, Simone Patergnani, David Larson, Kaitlyn Verbruggen, Mika Tanji, Laura Pellegrini, Valentina Signorato, Federica Olivetto, Sandra Pastorino, Masaki Nasu, Andrea Napolitano, Giovanni Gaudino, Paul Morris, Greg Sakamoto, Laura K Ferris, Alberto Danese, Andrea Raimondi, Carlo Tacchetti, Shafi Kuchay, Harvey I Pass, El Bachir Affar, Haining Yang, Paolo Pinton, Michele Carbone
BRCA1-associated protein 1 (BAP1) is a potent tumour suppressor gene that modulates environmental carcinogenesis. All carriers of inherited heterozygous germline BAP1-inactivating mutations (BAP1(+/-)) developed one and often several BAP1(-/-) malignancies in their lifetime, mostly malignant mesothelioma, uveal melanoma, and so on. Moreover, BAP1-acquired biallelic mutations are frequent in human cancers. BAP1 tumour suppressor activity has been attributed to its nuclear localization, where it helps to maintain genome integrity...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28612717/-paralogy-and-redundancy-maintaining-genome-integrity-during-v-d-j-recombination
#16
Chloé Lescale, Hélène Lenden Hasse, Ludovic Deriano
No abstract text is available yet for this article.
May 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28611731/the-genomic-architecture-of-novel-simulium-damnosum-wolbachia-prophage-sequence-elements-and-implications-for-onchocerciasis-epidemiology
#17
James L Crainey, Jacob Hurst, Poppy H L Lamberton, Robert A Cheke, Claire E Griffin, Michael D Wilson, Cláudia P Mendes de Araújo, María-Gloria Basáñez, Rory J Post
Research interest in Wolbachia is growing as new discoveries and technical advancements reveal the public health importance of both naturally occurring and artificial infections. Improved understanding of the Wolbachia bacteriophages (WOs) WOcauB2 and WOcauB3 [belonging to a sub-group of four WOs encoding serine recombinases group 1 (sr1WOs)], has enhanced the prospect of novel tools for the genetic manipulation of Wolbachia. The basic biology of sr1WOs, including host range and mode of genomic integration is, however, still poorly understood...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28611047/smurf2-mediated-stabilization-of-dna-topoisomerase-ii%C3%AE-controls-genomic-integrity
#18
Andrea Emanuelli, Aurora P Borroni, Liat Apel-Sarid, Pooja A Shah, Dhanoop Manikoth Ayyathan, Praveen Koganti, Gal Levy-Cohen, Michael Blank
DNA topoisomerase IIα (Topo IIα) ensures genomic integrity and unaltered chromosome inheritance and serves as a major target of several anticancer drugs. Topo IIα function is well understood, but how its expression is regulated remains unclear. Here we identify the E3 ubiquitin ligase Smurf2 as a physiological regulator of Topo IIα levels. Smurf2 physically interacted with Topo IIα and modified its ubiquitination status to protect Topo IIα from the proteasomal degradation in dose- and catalytically-dependent manners...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28609781/a-data-driven-structural-model-of-hssb1-nabp2-obfc2b-self-oligomerization
#19
Christine Touma, Mark N Adams, Nicholas W Ashton, Michael Mizzi, Serene El-Kamand, Derek J Richard, Liza Cubeddu, Roland Gamsjaeger
The maintenance of genome stability depends on the ability of the cell to repair DNA efficiently. Single-stranded DNA binding proteins (SSBs) play an important role in DNA processing events such as replication, recombination and repair. While the role of human single-stranded DNA binding protein 1 (hSSB1/NABP2/OBFC2B) in the repair of double-stranded breaks has been well established, we have recently shown that it is also essential for the base excision repair (BER) pathway following oxidative DNA damage. However, unlike in DSB repair, the formation of stable hSSB1 oligomers under oxidizing conditions is an important prerequisite for its proper function in BER...
June 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28605402/sparse-redundancy-analysis-of-high-dimensional-genetic-and-genomic-data
#20
Attila Csala, Frans P J M Voorbraak, Aeilko H Zwinderman, Michel H Hof
Motivation: Recent technological developments have enabled the possibility of genetic and genomic integrated data analysis approaches, where multiple omics data sets from various biological levels are combined and used to describe (disease) phenotypic variations. The main goal is to explain and ultimately predict phenotypic variations by understanding their genetic basis and the interaction of the associated genetic factors. Therefore, understanding the underlying geneticmechanisms of phenotypic variations is an ever increasing research interest in biomedical sciences...
June 12, 2017: Bioinformatics
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