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https://www.readbyqxmd.com/read/29149299/twj-screen-an-isothermal-screening-assay-to-assess-ligand-dna-junction-interactions-in-vitro
#1
Ludivine Guyon, Marc Pirrotta, Katerina Duskova, Anton Granzhan, Marie-Paule Teulade-Fichou, David Monchaud
The quest for chemicals able to operate at selected genomic loci in a spatiotemporally controlled manner is desirable to create manageable DNA damages. Mounting evidence now shows that alternative DNA structures, including G-quadruplexes and branched DNA (or DNA junctions), might hamper proper progression of replication fork, thus triggering DNA damages and genomic instability. Therefore, small molecules that stabilize these DNA structures are currently scrutinized as a promising way to create genomic defects that cannot be dealt with properly by cancer cells...
November 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29146938/computational-investigation-of-homologous-recombination-dna-repair-deficiency-in-sporadic-breast-cancer
#2
Yue Wang, Matthew H Ung, Sharon Cantor, Chao Cheng
BRCAness has important implications in the management and treatment of patients with breast and ovarian cancer. In this study, we propose a computational framework to measure the BRCAness of breast and ovarian tumor samples based on their gene expression profiles. We define a characteristic profile for BRCAness by comparing gene expression differences between BRCA1/2 mutant familial tumors and sporadic breast cancer tumors while adjusting for relevant clinical factors. With this BRCAness profile, our framework calculates sample-specific BRCA scores, which indicates homologous recombination (HR)-mediated DNA repair pathway activity of samples...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146814/natural-selection-shaped-the-rise-and-fall-of-passenger-pigeon-genomic-diversity
#3
Gemma G R Murray, André E R Soares, Ben J Novak, Nathan K Schaefer, James A Cahill, Allan J Baker, John R Demboski, Andrew Doll, Rute R Da Fonseca, Tara L Fulton, M Thomas P Gilbert, Peter D Heintzman, Brandon Letts, George McIntosh, Brendan L O'Connell, Mark Peck, Marie-Lorraine Pipes, Edward S Rice, Kathryn M Santos, A Gregory Sohrweide, Samuel H Vohr, Russell B Corbett-Detig, Richard E Green, Beth Shapiro
The extinct passenger pigeon was once the most abundant bird in North America, and possibly the world. Although theory predicts that large populations will be more genetically diverse, passenger pigeon genetic diversity was surprisingly low. To investigate this disconnect, we analyzed 41 mitochondrial and 4 nuclear genomes from passenger pigeons and 2 genomes from band-tailed pigeons, which are passenger pigeons' closest living relatives. Passenger pigeons' large population size appears to have allowed for faster adaptive evolution and removal of harmful mutations, driving a huge loss in their neutral genetic diversity...
November 17, 2017: Science
https://www.readbyqxmd.com/read/29146582/elucidation-of-the-two-h3k36me3-histone-methyltransferases-set2-and-ash1-in-fusarium-fujikuroi-unravels-their-different-chromosomal-targets-and-a-major-impact-of-ash1-on-genome-stability
#4
Slavica Janevska, Leonie Baumann, Christian M K Sieber, Martin Münsterkötter, Jonas Ulrich, Jörg Kämper, Ulrich Güldener, Bettina Tudzynski
In this work, we present a comprehensive analysis of the H3K36 histone methyltransferases Set2 and Ash1 in the filamentous ascomycete Fusarium fujikuroi In Saccharomyces cerevisiae, one single methyltransferase, Set2, confers all H3K36 methylation, while there are two members of the Set2 family in filamentous fungi, and even more H3K36 methyltransferases in higher eukaryotes. Whereas the yeast Set2 homolog has been analyzed in fungi previously, the second member of the Set2 family, designated Ash1, has not been described for any filamentous fungus...
November 16, 2017: Genetics
https://www.readbyqxmd.com/read/29145865/the-endonuclease-eepd1-mediates-synthetic-lethality-in-rad52-depleted-brca1-mutant-breast-cancer-cells
#5
Robert Hromas, Hyun-Suk Kim, Gurjit Sidhu, Elizabeth Williamson, Aruna Jaiswal, Taylor A Totterdale, Jocelyn Nole, Suk-Hee Lee, Jac A Nickoloff, Kimi Y Kong
BACKGROUND: Proper repair and restart of stressed replication forks requires intact homologous recombination (HR). HR at stressed replication forks can be initiated by the 5' endonuclease EEPD1, which cleaves the stalled replication fork. Inherited or acquired defects in HR, such as mutations in breast cancer susceptibility protein-1 (BRCA1) or BRCA2, predispose to cancer, including breast and ovarian cancers. In order for these HR-deficient tumor cells to proliferate, they become addicted to a bypass replication fork repair pathway mediated by radiation repair protein 52 (RAD52)...
November 16, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29144413/epstein-barr-virus-hijacks-dna-damage-response-transducers-to-orchestrate-its-life-cycle
#6
REVIEW
Pok Man Hau, Sai Wah Tsao
The Epstein-Barr virus (EBV) is a ubiquitous virus that infects most of the human population. EBV infection is associated with multiple human cancers, including Burkitt's lymphoma, Hodgkin's lymphoma, a subset of gastric carcinomas, and almost all undifferentiated non-keratinizing nasopharyngeal carcinoma. Intensive research has shown that EBV triggers a DNA damage response (DDR) during primary infection and lytic reactivation. The EBV-encoded viral proteins have been implicated in deregulating the DDR signaling pathways...
November 16, 2017: Viruses
https://www.readbyqxmd.com/read/29143133/association-of-dna-repair-genes-polymorphisms-and-mutations-with-increased-risk-of-head-and-neck-cancer-a-review
#7
REVIEW
Agata Dylawerska, Wojciech Barczak, Anna Wegner, Wojciech Golusinski, Wiktoria Maria Suchorska
DNA repair mechanisms allow maintain genomic stability and proper functioning within the cells. Any aberrations may cause an increased risk of many diseases such as cancer. The most crucial risk factors for head and neck squamous cell carcinoma are behavioral factors, predominantly chronic exposure to tobacco, alcohol addiction, and infection with human papillomavirus or Epstein-Barr virus. These agents can induce DNA damage; therefore, cells must activate appropriate mechanisms in order to function correctly...
November 15, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29141972/epigenetic-regulation-of-centromere-chromatin-stability-by-dietary-and-environmental-factors
#8
REVIEW
Diego Hernández-Saavedra, Rita S Strakovsky, Patricia Ostrosky-Wegman, Yuan-Xiang Pan
The centromere is a genomic locus required for the segregation of the chromosomes during cell division. This chromosomal region together with pericentromeres has been found to be susceptible to damage, and thus the perturbation of the centromere could lead to the development of aneuploidic events. Metabolic abnormalities that underlie the generation of cancer include inflammation, oxidative stress, cell cycle deregulation, and numerous others. The micronucleus assay, an early clinical marker of cancer, has been shown to provide a reliable measure of genotoxic damage that may signal cancer initiation...
November 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/29141455/methionine-adenosyltransferases-in-cancers-mechanisms-of-dysregulation-and-implications-for-therapy
#9
Lauren Y Maldonado, Diana Arsene, José M Mato, Shelly C Lu
Methionine adenosyltransferase genes encode enzymes responsible for the biosynthesis of S-adenosylmethionine, the principal biological methyl donor and precursor of polyamines and glutathione. Mammalian cells express three genes - MAT1A, MAT2A, and MAT2B - with distinct expression and functions. MAT1A is mainly expressed in the liver and maintains the differentiated states of both hepatocytes and bile duct epithelial cells. Conversely, MAT2A and MAT2B are widely distributed in non-parenchymal cells of the liver and extrahepatic tissues...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29139089/cancer-stem-cells-in-head-and-neck-carcinomas-identification-and-possible-therapeutic-implications
#10
Elize Wolmarans, Sonja C Boy, Sulette Nel, Anne E Mercier, Michael Sean Pepper
The recurrence and/or lack of response of certain tumors to radio- and chemotherapy has been attributed to a small subpopulation of cells termed cancer stem cells (CSCs). CSCs have been identified in many tumors (including solid and hematological tumors). CSCs are characterized by their capacity for self-renewal, their ability to introduce heterogeneity within a tumor mass and its metastases, genomic instability, and their insensitivity to both radiation and chemotherapy. The latter highlights the clinical importance of studying this subpopulation since their resistance to traditional treatments may lead to metastatic disease and/or tumor relapse...
November 15, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29137675/human-hyaluronic-acid-synthase-1-promotes-malignant-transformation-via-epithelial-to-mesenchymal-transition-micronucleation-and-centrosome-abnormalities
#11
Nguyet Nguyen, Awanit Kumar, Simi Chacko, Rodney J Ouellette, Anirban Ghosh
BACKGROUND: Human hyaluronic acid (HA) molecules are synthesized by three membrane spanning Hyaluronic Acid Synthases (HAS1, HAS2 and HAS3). Of the three, HAS1 is found to be localized more into the cytoplasmic space where it synthesizes intracellular HA. HA is a ubiquitous glycosaminoglycan, mainly present in the extracellular matrix (ECM) and on the cell surface, but are also detected intracellularly. Accumulation of HA in cancer cells, the cancer-surrounding stroma, and ECM is generally considered an independent prognostic factors for patients...
November 14, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29137223/hormone-induced-dna-damage-response-and-repair-mediated-by-cyclin-d1-in-breast-and-prostate-cancer
#12
REVIEW
Gabriele Di Sante, Agnese Di Rocco, Claudia Pupo, Mathew C Casimiro, Richard G Pestell
Cell cycle control proteins govern events that leads to the production of two identical daughter cells. Distinct sequential temporal phases, Gap 1 (G1), Gap 0 (G0), Synthesis (S), Gap 2 (G2) and Mitosis (M) are negotiated through a series of check points during which the favorability of the local cellular environment is assessed, prior to replicating DNA [1]. Cyclin D1 has been characterized as a key regulatory subunit of the holoenzyme that promotes the G1/S-phase transition through phosphorylating the pRB protein...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133916/brca2-antagonizes-classical-and-alternative-nonhomologous-end-joining-to-prevent-gross-genomic-instability
#13
Jinhua Han, Chunyan Ruan, Michael S Y Huen, Jiadong Wang, Anyong Xie, Chun Fu, Ting Liu, Jun Huang
BRCA2-deficient cells exhibit gross genomic instability, but the underlying mechanisms are not fully understood. Here we report that inactivation of BRCA2 but not RAD51 destabilizes RPA-coated single-stranded DNA (ssDNA) structures at resected DNA double-strand breaks (DSBs) and greatly enhances the frequency of nuclear fragmentation following cell exposure to DNA damage. Importantly, these BRCA2-associated deficits are fueled by the aberrant activation of classical (c)- and alternative (alt)- nonhomologous end-joining (NHEJ), and rely on the well-defined DNA damage signaling pathway involving the pro-c-NHEJ factor 53BP1 and its downstream effector RIF1...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29132683/-impairment-of-dna-damage-response-and-cancer
#14
REVIEW
Chloé Rancoule, Alexis Vallard, Jean-Baptiste Guy, Sophie Espenel, Sylvie Sauvaigo, Claire Rodriguez-Lafrasse, Nicolas Magné
Maintaining the genetic integrity is a key process in cell viability and is enabled by a wide network of repair pathways. When this system is defective, it generates genomic instability and results in an accumulation of chromosomal aberrations and mutations that may be responsible for various clinical phenotypes, including susceptibility to develop cancer. Indeed, these defects can promote not only the initiation of cancer, but also allow the tumor cells to rapidly acquire mutations during their evolution. Several genes are involved in these damage repair systems and particular polymorphisms are predictive of the onset of cancer, the best described of them being BRCA...
November 10, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29132681/-dna-repair-as-a-therapeutic-target
#15
REVIEW
Lauriane Eberst, Medhi Brahmi, Philippe A Cassier
The transmission of an intact and stable genetic code at each cell division relies on different DNA repair systems. Germline mutations of some of these genes cause cancer predisposition, whereas somatic mutations are frequently found in various cancer types, generating genomic instability. As a consequence, cancer cell becomes more susceptible to additional DNA damage. Pharmacological inhibition of DNA repair pathways exploits this frailty: it triggers more damages than cancer cell can tolerate, finally leading to apoptosis...
November 10, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29132324/caismov24-a-new-human-low-grade-serous-ovarian-carcinoma-cell-line
#16
Rodrigo Fernandes da Silva, Daniela Maira Cardozo, Gisele Olinto Libanio Rodrigues, Caroline Natânia de Souza-Araújo, Natacha Azussa Migita, Liliana Aparecida Lucci de Angelo Andrade, Sophie Derchain, José Andrés Yunes, Fernando Guimarães
BACKGROUND: The spontaneous immortalization of primary malignant cells is frequently assigned to their genetic instability during in vitro culturing. In this study, the new epithelial ovarian cancer cell line CAISMOV24 was described and compared with its original low-grade serous ovarian carcinoma. METHODS: The in vitro culture was established with cells isolated from ascites of a 60-year-old female patient with recurrent ovarian cancer. The CAISMOV24 line was assessed for cell growth, production of soluble biomarkers, expression of surface molecules and screened for typical mutations found in serous ovarian carcinoma...
November 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29129532/idiosyncratic-genome-degradation-in-a-bacterial-endosymbiont-of-periodical-cicadas
#17
Matthew A Campbell, Piotr Łukasik, Chris Simon, John P McCutcheon
When a free-living bacterium transitions to a host-beneficial endosymbiotic lifestyle, it almost invariably loses a large fraction of its genome [1, 2]. The resulting small genomes often become stable in size, structure, and coding capacity [3-5], as exemplified by Sulcia muelleri, a nutritional endosymbiont of cicadas. Sulcia's partner endosymbiont, Hodgkinia cicadicola, similarly remains co-linear in some cicadas diverged by millions of years [6, 7]. But in the long-lived periodical cicada Magicicada tredecim, the Hodgkinia genome has split into dozens of tiny, gene-sparse circles that sometimes reside in distinct Hodgkinia cells [8]...
November 2, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29127260/an-improved-brome-mosaic-virus-silencing-vector-greater-insert-stability-and-more-extensive-vigs
#18
Xin Shun Ding, Stephen W Mannas, Bethany A Bishop, Xiaolan Rao, Mitchell Lecoultre, Soonil Kwon, Richard S Nelson
Virus-induced gene silencing (VIGS) is used extensively for gene function studies in plants. VIGS is inexpensive and rapid compared with silencing conducted through stable transformation, but many virus silencing vectors, especially in grasses, induce only transient silencing phenotypes. A major reason for transient phenotypes is instability of the foreign gene fragment (insert) in the vector during VIGS. Here we report the development of a Brome mosaic virus (BMV)-based vector that better maintains inserts through modification of the original BMV vector RNA sequence...
November 10, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29126329/effect-of-benzo-a-pyrene-on-spindle-mis-orientation-and-fidelity-of-chromosome-segregation-in-lung-epithelial-beas-2b-cells
#19
Jose Thaiparambil, Oula Mansour, Randa El-Zein
Benzo[a]pyrene (B[a]P) is an environmental carcinogen found in tobacco smoke. It leads to high levels of DNA adducts in the lungs of cigarette smokers contributing to genomic instability. Alterations in the mitotic spindle apparatus play a major role in the generation of genomic instability through promoting chromosome mis-segregation and aneuploidy. To date, the effect of B[a]P exposure on altering the mitotic apparatus in normal lung epithelial cells remains unknown. In our study, BEAS-2B human bronchial epithelial cells were exposed to B[a]P and spindle dynamics were evaluated...
November 6, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29125140/mouse-embryonic-stem-cells-have-increased-capacity-for-replication-fork-restart-driven-by-the-specific-filia-floped-protein-complex
#20
Bo Zhao, Weidao Zhang, Yixian Cun, Jingzheng Li, Yan Liu, Jing Gao, Hongwen Zhu, Hu Zhou, Rugang Zhang, Ping Zheng
Pluripotent stem cells (PSCs) harbor constitutive DNA replication stress during their rapid proliferation and the consequent genome instability hampers their applications in regenerative medicine. It is therefore important to understand the regulatory mechanisms of replication stress response in PSCs. Here, we report that mouse embryonic stem cells (ESCs) are superior to differentiated cells in resolving replication stress. Specifically, ESCs utilize a unique Filia-Floped protein complex-dependent mechanism to efficiently promote the restart of stalled replication forks, therefore maintaining genomic stability...
November 10, 2017: Cell Research
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