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Genomic instability

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https://www.readbyqxmd.com/read/28921524/karyotype-variation-of-cho-host-cell-lines-over-time-in-culture-characterized-by-chromosome-counting-and-chromosome-painting
#1
Sabine Vcelar, Vaibhav Jadhav, Michael Melcher, Norbert Auer, Astrid Hrdina, Rebecca Sagmeister, Kelley Heffner, Anja Puklowski, Michael Betenbaugh, Till Wenger, Friedrich Leisch, Martina Baumann, Nicole Borth
Genomic rearrangements are a common phenomenon in rapidly growing cell lines such as Chinese hamster ovary (CHO) cells, a feature that in the context of production of biologics may lead to cell line and product instability. Few methods exist to assess such genome wide instability. Here we use the population distribution of chromosome numbers per cell as well as chromosome painting to quantify the karyotypic variation in several CHO host cell lines. CHO-S, CHO-K1 8mM glutamine and CHO-K1 cells adapted to grow in media containing no glutamine were analyzed over up to 6 months in culture...
September 16, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28920961/germline-mutations-affecting-the-histone-h4-core-cause-a-developmental-syndrome-by-altering-dna-damage-response-and-cell-cycle-control
#2
Federico Tessadori, Jacques C Giltay, Jane A Hurst, Maarten P Massink, Karen Duran, Harmjan R Vos, Robert M van Es, Richard H Scott, Koen L I van Gassen, Jeroen Bakkers, Gijs van Haaften
Covalent modifications of histones have an established role as chromatin effectors, as they control processes such as DNA replication and transcription, and repair or regulate nucleosomal structure. Loss of modifications on histone N tails, whether due to mutations in genes belonging to histone-modifying complexes or mutations directly affecting the histone tails, causes developmental disorders or has a role in tumorigenesis. More recently, modifications affecting the globular histone core have been uncovered as being crucial for DNA repair, pluripotency and oncogenesis...
September 18, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28918520/derivation-of-human-induced-pluripotent-stem-cell-ipsc-lines-and-mechanism-of-pluripotency-historical-perspective-and-recent-advances
#3
REVIEW
Arvind Chhabra
Derivation of human embryonic stem cell (hES) lines in 1998 was not only a major technological breakthrough in the field of regenerative medicine; it also triggered a passionate debate about the ethical issues associated with the utilization of human embryos for derivation of hESC lines. Successful derivation of induced pluripotent stem cell (iPS) lines from human somatic cells with defined reprogramming factors by Shinya Yamanaka`s group in 2007 was another breakthrough that generated enormous excitement and hope for the development of donor-specific personalized cell replacement therapies (CRT) without the ethical dilemma associated with it...
September 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28916651/escherichia-coli-and-neisseria-gonorrhoeae-uvrd-helicase-unwinds-g4-dna-structures
#4
Kaustubh Shukla, Roshan Thakur, Debayan Ganguli, Desirazu Rao, Ganesh Nagaraju
G-quadruplex (G4) secondary structures have been implicated in various biological processes including gene expression, DNA replication and telomere maintenance. However, unresolved G4 structures impede replication progression which can lead to generation of DNA double-strand breaks and genome instability. Helicases have been shown to resolve G4 structures to facilitate faithful duplication of the genome. Escherichia coli UvrD (EcUvrD) helicase plays a crucial role in nucleotide excision repair, mismatch repair and in the regulation of homologous recombination...
September 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28915699/biological-effects-and-epidemiological-consequences-of-arsenic-exposure-and-reagents-that-can-ameliorate-arsenic-damage-in-vivo
#5
REVIEW
Chinthalapally V Rao, Sanya Pal, Altaf Mohammed, Mudassir Farooqui, Mark P Doescher, Adam S Asch, Hiroshi Y Yamada
Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide "hot spots" where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914798/genome-instability-and-%C3%AE-h2ax
#6
REVIEW
Anastasios Georgoulis, Constantinos E Vorgias, George P Chrousos, Emmy P Rogakou
γH2AX has emerged in the last 20 years as a central player in the DDR (DNA damage response), with specificity for DSBs (double-strand breaks). Upon the generation of DSBs, γ-phosphorylation extends along megabase-long domains in chromatin, both sides of the damage. The significance of this mechanism is of great importance; it depicts a biological amplification mechanism where one DSB induces the γ-phosphorylation of thousands of H2AX molecules along megabaselong domains of chromatin, that are adjusted to the sites of DSBs...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28913947/extreme-chromosome-17-copy-number-instability-is-a-prognostic-factor-in-patients-with-gastroesophageal-adenocarcinoma-a-retrospective-cohort-study
#7
Jacqueline E Birkness, Neal G Spada, Caitlyn Miller, James D Luketich, Katie S Nason, Weijing Sun, Jon M Davison
Gastric and esophageal cancers frequently show genomic instability and aneuploidy. Chromosomal copy number instability (CIN) is a form of genomic instability that exerts pleiotropic effects on cellular biology and is a source of genetic heterogeneity in a population of cells. CIN results in cell-to-cell variation in chromosome copy number which can be detected and quantified by fluorescence in situ hybridization (FISH). CIN is a biomarker associated with differential response to a number of chemotherapy compounds...
September 14, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28912486/the-homologous-recombination-machinery-orchestrates-post-replication-dna-repair-during-self-renewal-of-mouse-embryonic-stem-cells
#8
Eui-Hwan Choi, Seobin Yoon, Kyung-Soon Park, Keun P Kim
Embryonic stem (ES) cells require homologous recombination (HR) to cope with genomic instability caused during self-renewal. Here, we report expression dynamics and localization of endogenous HR factors in DNA break repair of ES cells. In addition, we analyzed gene expression patterns of HR-related factors at the transcript level with RNA-sequencing experiments. We showed that ES cells constitutively expressed diverse HR proteins throughout the cell cycle and that HR protein expression was not significantly changed even in the DNA damaging conditions...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912372/genome-wide-maps-of-alkylation-damage-repair-and-mutagenesis-in-yeast-reveal-mechanisms-of-mutational-heterogeneity
#9
Peng Mao, Alexander J Brown, Ewa P Malc, Piotr A Mieczkowski, Michael J Smerdon, Steven A Roberts, John J Wyrick
DNA base damage is an important contributor to genome instability, but how the formation and repair of these lesions is affected by the genomic landscape and contributes to mutagenesis is unknown. Here, we describe genome-wide maps of DNA base damage, repair, and mutagenesis at single nucleotide resolution in yeast treated with the alkylating agent methyl methanesulfonate (MMS). Analysis of these maps revealed that base excision repair (BER) of alkylation damage is significantly modulated by chromatin, with faster repair in nucleosome-depleted regions, and slower repair and higher mutation density within strongly positioned nucleosomes...
September 14, 2017: Genome Research
https://www.readbyqxmd.com/read/28910671/delayed-effects-of-accelerated-heavy-ions-on-the-induction-of-hprt-mutations-in-v79-hamster-cells
#10
Pavel Bláha, Nataliya A Koshlan, Igor V Koshlan, Daria V Petrova, Yulia V Bogdanova, Raisa D Govorun, Viliam Múčka, Evgeny A Krasavin
Fundamental research on the harmful effects of ionizing radiation on living cells continues to be of great interest. Recently, priority has been given to the study of high-charge and high-energy (HZE) ions that comprise a substantial part of the galactic cosmic ray (GCR) spectra that would be encountered during long-term space flights. Moreover, predictions of the delayed genetic effects of high linear energy transfer (LET) exposure is becoming more important as heavy ion therapy use is increasing. This work focuses mainly on the basic research on the delayed effects of HZE ions on V79 Chinese hamster cells, with emphasis on the induction of HPRT mutations after prolonged expression times (ET)...
August 31, 2017: Mutation Research
https://www.readbyqxmd.com/read/28903902/single-cell-gene-variation-analysis-method-for-single-gland
#11
Yan Zhou, Chao-Jie Wang, Chun-Chao Zhu, Jiang-Rong Chen, Ming Cheng, Yu-Liang Deng, Yan Guo
Single-cell analysis of heterogeneity has become the cutting-edge technology for profound understandings of relationships between cell populations. At present, common methods used in single cellular genomic research are mainly microfluidic technologies (Fluidigm) or based on microwells, both requiring a uniform size of cells at the entrance. However, the size of cells in specific tissues can vary from type to type. To address this issue, we need to establish a method to identify genomic features of individual cells of different sizes...
August 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28903359/expression-of-sialyl-tn-sugar-antigen-in-bladder-cancer-cells-affects-response-to-bacillus-calmette-gu%C3%A3-rin-bcg-and-to-oxidative-damage
#12
Paulo F Severino, Mariana Silva, Mylene Carrascal, Nadia Malagolini, Mariella Chiricolo, Giulia Venturi, Annalisa Astolfi, Mariangela Catera, Paula A Videira, Fabio Dall'Olio
The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. A poorly understood correlation between the expression of sTn and BC patient's response to BCG was previously observed. By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902865/optimization-of-the-expression-purification-and-polymerase-activity-reaction-conditions-of-recombinant-human-primpol
#13
Elizaveta O Boldinova, Gorazd Stojkovič, Rafil Khairullin, Sjoerd Wanrooij, Alena V Makarova
Human PrimPol is a DNA primase/polymerase involved in DNA damage tolerance and prevents nuclear genome instability. PrimPol is also localized to the mitochondria, but its precise function in mitochondrial DNA maintenance has remained elusive. PrimPol works both as a translesion (TLS) polymerase and as the primase that restarts DNA replication after a lesion. However, the observed biochemical activities of PrimPol vary considerably between studies as a result of different reaction conditions used. To reveal the effects of reaction composition on PrimPol DNA polymerase activity, we tested the polymerase activity in the presence of various buffer agents, salt concentrations, pH values and metal cofactors...
2017: PloS One
https://www.readbyqxmd.com/read/28900487/chromosomal-and-genomic-variations-in-esophageal-squamous-cell-carcinoma-a-review-of-technologies-applications-and-prospections
#14
REVIEW
Qi Song, Dongxian Jiang, Haixing Wang, Jie Huang, Yalan Liu, Chen Xu, Yingyong Hou
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor prognosis worldwide. The poor prognosis is due to the advanced stage at the time of diagnosis and the limited clinical staging lacking significant molecular biomarkers to effectively stratify patients for treatment options. As cancer is a disease of genome instability and a resulting of accumulation of genetic alteration, mounting chromosomal and genomic technologies were developed and progressed rapidly which could be used for characterizing patients in genomics level...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28898985/lineage-switch-between-b-lymphoblastic-leukemia-and-acute-myeloid-leukemia-intermediated-by-occult-myelodysplastic-neoplasm-two-cases-of-adult-patients-with-evidence-of-genomic-instability-and-clonal-selection-by-chemotherapy
#15
Bin Wu, Rachel Jug, Catherine Luedke, Pu Su, Catherine Rehder, Chad McCall, Anand S Lagoo, Endi Wang
Objectives: Lineage switch occurs in rare leukemias, and the mechanism is unclear. We report two cases of B-lymphoblastic leukemia (B-ALL) relapsed as acute myeloid leukemia (AML). Methods: Retrospective review of clinical and laboratory data. Results: Complex cytogenetic abnormalities were detected in B-ALL for both cases with subclone heterogeneity. Postchemotherapy marrow biopsies showed trilineage hematopoiesis without detectable B-ALL...
August 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28898877/identification-of-small-and-non-small-cell-lung-cancer-markers-in-peripheral-blood-using-cytokinesis-blocked-micronucleus-and-spectral-karyotyping-assays
#16
Randa A El-Zein, Shereen Abdel-Rahman, Kyle J Santee, Robert Yu, Sanjay Shete
Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer. There is an urgent need to develop tools to identify individuals at high risk of developing SCLC. We have previously reported that the cytokinesis-blocked micronucleus (CBMN) assay is a strong predictor of non-small cell lung cancer (NSCLC). Here, we investigate the sensitivity of the CBMN endpoints as predictors of SCLC risk. We conducted the CBMN assay on SCLC patients (n = 216), NSCLC patients (n = 173), and healthy controls (n = 204)...
September 13, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28894962/ring-chromosomes-from-formation-to-clinical-potential
#17
REVIEW
Inna E Pristyazhnyuk, Aleksei G Menzorov
Ring chromosomes (RCs) are circular DNA molecules, which occur rarely in eukaryotic nuclear genomes. Lilian Vaughan Morgan first described them in the fruit fly. Human embryos very seldom have RCs, about 1:50,000. Carriers of RCs may have varying degrees of symptoms, from healthy phenotype to serious pathologies in physical and intellectual development. Many authors describe common symptoms of RC presence: short stature and some developmental delay that could be described as a "ring chromosome syndrome." As a rule, RCs arise de novo through the end-joining of two DNA double-strand breaks, telomere-subtelomere junction, or inv dup del rearrangement in both meiosis and mitosis...
September 12, 2017: Protoplasma
https://www.readbyqxmd.com/read/28894253/atm-deficiency-increases-genomic-instability-and-metastatic-potential-in-a-mouse-model-of-pancreatic-cancer
#18
Yiannis Drosos, David Escobar, Ming-Yi Chiang, Kathryn Roys, Virginia Valentine, Marc B Valentine, Jerold E Rehg, Vaibhav Sahai, Lesa A Begley, Jianming Ye, Leena Paul, Peter J McKinnon, Beatriz Sosa-Pineda
Germline mutations in ATM (encoding the DNA-damage signaling kinase, ataxia-telangiectasia-mutated) increase Familial Pancreatic Cancer (FPC) susceptibility, and ATM somatic mutations have been identified in resected human pancreatic tumors. Here we investigated how Atm contributes to pancreatic cancer by deleting this gene in a murine model of the disease expressing oncogenic Kras (Kras(G12D)). We show that partial or total ATM deficiency cooperates with Kras(G12D) to promote highly metastatic pancreatic cancer...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894029/pari-regulates-stalled-replication-fork-processing-to-maintain-genome-stability-upon-replication-stress-in-mice
#19
Ayako L Mochizuki, Ami Katanaya, Eri Hayashi, Mihoko Hosokawa, Emiko Moribe, Akira Motegi, Masamichi Ishiai, Minoru Takata, Gen Kondoh, Hitomi Watanabe, Norio Nakatsuji, Shinichiro Chuma
DNA replication is frequently perturbed by intrinsic as well as extrinsic genotoxic stress. At damaged forks, DNA replication and repair activities require proper coordination to maintain the genome integrity. We show here that PARI anti-recombinase plays an essential role to modulate the initial response to replication stress in mice. PARI is functionally dormant at replisomes during normal replication, but upon replication stress, it enhances nascent strand shortening that is regulated by RAD51 and MRE11...
September 11, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28893936/take-your-pikk-tumour-viruses-and-dna-damage-response-pathways
#20
REVIEW
Neha J Pancholi, Alexander M Price, Matthew D Weitzman
Viruses regulate cellular processes to facilitate viral replication. Manipulation of nuclear proteins and pathways by nuclear replicating viruses often causes cellular genome instability that contributes to transformation. The cellular DNA damage response (DDR) safeguards the host to maintain genome integrity, but DNA tumour viruses can manipulate the DDR to promote viral propagation. In this review, we describe the interactions of DNA tumour viruses with the phosphatidylinositol 3-kinase-like protein kinase (PIKK) pathways, which are central regulatory arms of the DDR...
October 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
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