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https://www.readbyqxmd.com/read/28819832/protective-role-of-humic-acids-against-picloram-induced-genomic-instability-and-dna-methylation-in-phaseolus-vulgaris
#1
Mahmut Sinan Taspinar, Murat Aydin, Burcu Sigmaz, Nalan Yildirim, Guleray Agar
Picloram (4-amino-3,5,6-trichloropicolinic acid) is a liquid auxinic herbicide used to control broad-leaved weeds. Picloram is representing a possible hazard to ecosystems and human health. Therefore, in this study, DNA methylation changes and DNA damage levels in Phaseolus vulgaris exposed to picloram, as well as whether humic acid (HA) has preventive effects on these changes were investigated. Random amplified polymorphic DNA (RAPD) techniques were used for identification of DNA damage and coupled restriction enzyme digestion-random amplification (CRED-RA) techniques were used to detect the changed pattern of DNA methylation...
August 17, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28819201/linker-histone-h1-prevents-r-loop-accumulation-and-genome-instability-in-heterochromatin
#2
Aleix Bayona-Feliu, Anna Casas-Lamesa, Oscar Reina, Jordi Bernués, Fernando Azorín
Linker histone H1 is an important structural component of chromatin that stabilizes the nucleosome and compacts the nucleofilament into higher-order structures. The biology of histone H1 remains, however, poorly understood. Here we show that Drosophila histone H1 (dH1) prevents genome instability as indicated by the increased γH2Av (H2AvS137P) content and the high incidence of DNA breaks and sister-chromatid exchanges observed in dH1-depleted cells. Increased γH2Av occurs preferentially at heterochromatic elements, which are upregulated upon dH1 depletion, and is due to the abnormal accumulation of DNA:RNA hybrids (R-loops)...
August 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28819127/multiple-e3s-promote-the-degradation-of-histone-h3-variant-cse4
#3
Haili Cheng, Xin Bao, Xin Gan, Shiwen Luo, Hai Rao
The histone H3-like protein Cse4/CENP-A acts as a key molecular marker that differentiates the special centromeric chromatin structures from bulk nucleosomes. As altered Cse4/CENP-A activity leads to genome instability, it is pivotal to understand the mechanism underlying Cse4 regulation. Here, we demonstrate that four ubiquitin ligases (i.e., Ubr1, Slx5, Psh1, and Rcy1) work in parallel to promote Cse4 turnover in yeast. Interestingly, Cse4 overexpression leads to cellular toxicity and cell cycle delay in yeast cells lacking PSH1, but not in cells lacking UBR1, suggesting different roles of these two degradation pathways...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819029/loss-of-the-tumor-suppressor-stag2-promotes-telomere-recombination-and-extends-the-replicative-lifespan-of-normal-human-cells
#4
Zharko Daniloski, Susan Smith
Sister chromatids are held together by cohesin, a tripartite ring with a peripheral SA1/2 subunit, where SA1 is required for telomere cohesion and SA2 for centromere cohesion. The STAG2 gene encoding SA2 is often inactivated in human cancer, but not in in a manner associated with aneuploidy. Thus, how these tumors maintain chromosomal cohesion and how STAG2 loss contributes to tumorigenesis remain open questions. Here we show that, despite a loss in centromere cohesion, sister chromatids in STAG2 mutant tumor cells maintain cohesion in mitosis at chromosome arms and telomeres...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28819025/mre11-promotes-tumorigenesis-by-facilitating-resistance-to-oncogene-induced-replication-stress
#5
Elizabeth Spehalski, Kayla M Capper, Cheryl J Smith, Mary J Morgan, Maria Dinkelmann, Jeffrey Buis, JoAnn M Sekiguchi, David O Ferguson
Hypomorphic mutations in the genes encoding the MRE11/RAD50/NBS1 (MRN) DNA repair complex lead to cancer-prone syndromes. MRN binds DNA double strand breaks where it functions in repair and triggers cell cycle checkpoints via activation of the ataxia-telangiectasia mutated (ATM) kinase. To gain understanding of MRN in cancer, we engineered mice with B lymphocytes lacking MRN, or harboring MRN in which MRE11 lacks nuclease activities. Both forms of MRN deficiency led to hallmarks of cancer, including oncogenic translocations involving c-Myc and the immunoglobulin locus...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818973/mutations-in-the-promoter-of-the-telomerase-gene-tert-contribute-to-tumorigenesis-by-a-two-step-mechanism
#6
Kunitoshi Chiba, Franziska K Lorbeer, A Hunter Shain, David T McSwiggen, Eva Schruf, Areum Oh, Jekwan Ryu, Xavier Darzacq, Boris C Bastian, Dirk Hockemeyer
TERT promoter mutations (TPMs) are the most common non-coding mutations in cancer. The timing and consequences of TPMs have not been fully established. Here we show that TPMs acquired at the transition from benign nevus to malignant melanoma do not support telomere maintenance. In vitro experiments revealed that TPMs do not prevent telomere attrition, resulting in cells with critically short and unprotected telomeres. Immortalization by TPMs requires a gradual upregulation of telomerase, coinciding with telomere fusions...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28818866/systematic-identification-of-determinants-for-single-strand-annealing-mediated-deletion-formation-in-saccharomyces-cerevisiae
#7
Maia Segura-Wang, Megumi Onishi-Seebacher, Adrian M Stütz, Balca R Mardin, Jan O Korbel
To ensure genomic integrity, living organisms have evolved diverse molecular processes for sensing and repairing damaged DNA. If improperly repaired, DNA damage can give rise to different types of mutations, an important class of which are the genomic structural variants (SVs). In spite of their importance for phenotypic variation and genome evolution, potential contributors to SV formation in Saccharomyces cerevisiae (budding yeast), a highly tractable model organism, are not fully recognized. Here we developed and applied a genome-wide assay to identify yeast gene knock-out mutants associated with de novo deletion formation, in particular single strand annealing (SSA) -mediated deletion formation in a systematic manner...
August 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28815541/long-noncoding-rnas-in-cancer-and-therapeutic-potential
#8
Arun Renganathan, Emanuela Felley-Bosco
Long noncoding RNAs (lncRNAs) are the major elements of the mammalian transcriptome that is emerging as a central player controlling diverse cellular mechanisms. Most of the well-studied lncRNAs so far are found to be crucial in regulating cellular processes such as cell cycle, growth, and apoptosis that ensure homeostasis. Owing to their location and distribution in the genome, lncRNAs influence the transcription of a wide range of proteins directly or indirectly by transcriptional and posttranscriptional alterations, which opens up the "LncRNA-cancer paradigm" in a context-dependent manner, i...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814522/characterization-of-cis-acting-rna-elements-of-zika-virus-by-using-a-self-splicing-ribozyme-dependent-infectious-clone
#9
Zhong-Yu Liu, Jiu-Yang Yu, Xing-Yao Huang, Hang Fan, Xiao-Feng Li, Yong-Qiang Deng, Xue Ji, Meng-Li Cheng, Qing Ye, Hui Zhao, Jian-Feng Han, Xiao-Ping An, Tao Jiang, Bo Zhang, Yi-Gang Tong, Cheng-Feng Qin
Zika virus (ZIKV) has caused significant outbreaks and epidemics in the Americas recently, raising global concern due to its ability to cause microcephaly and other neurological complications. A stable and efficient infectious clone of ZIKV is urgently needed. However, the instability and toxicity of flavivirus cDNA clones in E. coli hosts has hindered the development of ZIKV infectious clones. Herein, using a novel self-splicing ribozyme-based strategy, we have generated a stable infectious cDNA clone of a contemporary ZIKV strain imported from Venezuela to China in 2016...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814448/carcinogen-susceptibility-is-regulated-by-genome-architecture-and-predicts-cancer-mutagenesis
#10
Pablo E García-Nieto, Erin K Schwartz, Devin A King, Jonas Paulsen, Philippe Collas, Rafael E Herrera, Ashby J Morrison
The development of many sporadic cancers is directly initiated by carcinogen exposure. Carcinogens induce malignancies by creating DNA lesions (i.e., adducts) that can result in mutations if left unrepaired. Despite this knowledge, there has been remarkably little investigation into the regulation of susceptibility to acquire DNA lesions. In this study, we present the first quantitative human genome-wide map of DNA lesions induced by ultraviolet (UV) radiation, the ubiquitous carcinogen in sunlight that causes skin cancer...
August 16, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28813500/telomere-biology-and-telomerase-mutations-in-cirrhotic-patients-with-hepatocellular-carcinoma
#11
Flávia S Donaires, Natália F Scatena, Raquel M Alves-Paiva, Joshua D Podlevsky, Dhenugen Logeswaran, Barbara A Santana, Andreza C Teixeira, Julian J-L Chen, Rodrigo T Calado, Ana L C Martinelli
Telomeres are repetitive DNA sequences at linear chromosome termini, protecting chromosomes against end-to-end fusion and damage, providing chromosomal stability. Telomeres shorten with mitotic cellular division, but are maintained in cells with high proliferative capacity by telomerase. Loss-of-function mutations in telomere-maintenance genes are genetic risk factors for cirrhosis development in humans and murine models. Telomerase deficiency provokes accelerated telomere shortening and dysfunction, facilitating genomic instability and oncogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28812991/the-retinoblastoma-rb-tumor-suppressor-pushing-back-against-genome-instability-on-multiple-fronts
#12
REVIEW
Renier Vélez-Cruz, David G Johnson
The retinoblastoma (RB) tumor suppressor is known as a master regulator of the cell cycle. RB is mutated or functionally inactivated in the majority of human cancers. This transcriptional regulator exerts its function in cell cycle control through its interaction with the E2F family of transcription factors and with chromatin remodelers and modifiers that contribute to the repression of genes important for cell cycle progression. Over the years, studies have shown that RB participates in multiple processes in addition to cell cycle control...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28812736/the-evolution-and-population-diversity-of-human-specific-segmental-duplications
#13
Megan Y Dennis, Lana Harshman, Bradley J Nelson, Osnat Penn, Stuart Cantsilieris, John Huddleston, Francesca Antonacci, Kelsi Penewit, Laura Denman, Archana Raja, Carl Baker, Kenneth Mark, Maika Malig, Nicolette Janke, Claudia Espinoza, Holly A F Stessman, Xander Nuttle, Kendra Hoekzema, Tina A Lindsay-Graves, Richard K Wilson, Evan E Eichler
Segmental duplications contribute to human evolution, adaptation and genomic instability but are often poorly characterized. We investigate the evolution, genetic variation and coding potential of human-specific segmental duplications (HSDs). We identify 218 HSDs based on analysis of 322 deeply sequenced archaic and contemporary hominid genomes. We sequence 550 human and nonhuman primate genomic clones to reconstruct the evolution of the largest, most complex regions with protein-coding potential (N = 80 genes from 33 gene families)...
February 17, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28811338/emerging-functions-of-the-fanconi-anemia-pathway-at-a-glance
#14
REVIEW
Rhea Sumpter, Beth Levine
Fanconi anemia (FA) is a rare disease, in which homozygous or compound heterozygous inactivating mutations in any of 21 genes lead to genomic instability, early-onset bone marrow failure and increased cancer risk. The FA pathway is essential for DNA damage response (DDR) to DNA interstrand crosslinks. However, proteins of the FA pathway have additional cytoprotective functions that may be independent of DDR. We have shown that many FA proteins participate in the selective autophagy pathway that is required for the destruction of unwanted intracellular constituents...
August 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28809811/mutation-clusters-from-cancer-exome
#15
Zura Kakushadze, Willie Yu
We apply our statistically deterministic machine learning/clustering algorithm *K-means (recently developed in https://ssrn.com/abstract=2908286) to 10,656 published exome samples for 32 cancer types. A majority of cancer types exhibit a mutation clustering structure. Our results are in-sample stable. They are also out-of-sample stable when applied to 1389 published genome samples across 14 cancer types. In contrast, we find in- and out-of-sample instabilities in cancer signatures extracted from exome samples via nonnegative matrix factorization (NMF), a computationally-costly and non-deterministic method...
August 15, 2017: Genes
https://www.readbyqxmd.com/read/28808622/radiation-exposure-and-reduction-in-the-operating-room-perspectives-and-future-directions-in-spine-surgery
#16
REVIEW
Ankur S Narain, Fady Y Hijji, Kelly H Yom, Krishna T Kudaravalli, Brittany E Haws, Kern Singh
Intraoperative imaging is vital for accurate placement of instrumentation in spine surgery. However, the use of biplanar fluoroscopy and other intraoperative imaging modalities is associated with the risk of significant radiation exposure in the patient, surgeon, and surgical staff. Radiation exposure in the form of ionizing radiation can lead to cellular damage via the induction of DNA lesions and the production of reactive oxygen species. These effects often result in cell death or genomic instability, leading to various radiation-associated pathologies including an increased risk of malignancy...
July 18, 2017: World Journal of Orthopedics
https://www.readbyqxmd.com/read/28808044/germline-mutation-contribution-to-chromosomal-instability
#17
REVIEW
Sock Hoai Chan, Joanne Ngeow
Genomic instability is a feature of cancer that fuels oncogenesis through increased frequency of genetic disruption, leading to loss of genomic integrity and promoting clonal evolution as well as tumor transformation. A form of genomic instability prevalent across cancer types is chromosomal instability, which involves karyotypic changes including chromosome copy number alterations as well as gross structural abnormalities such as transversions and translocations. Defects in cellular mechanisms that are in place to govern fidelity of chromosomal segregation, DNA repair and ultimately genomic integrity are known to contribute to chromosomal instability...
September 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28807210/personalized-treatment-in-patients-with-colorectal-liver-metastases
#18
Dimitrios Moris, Timothy M Pawlik
BACKGROUND: Precision Medicine Initiative is a new research effort aiming to offer personalized treatment in many diseases, including cancer. The aim of the present article is to offer novel insights about the role of personalized treatment in patients with colorectal liver metastases (CRLM). METHODS: A review of the literature regarding personalized medicine and colorectal liver metastases was performed mainly in the MEDLINE/PubMed database. RESULTS: Surgical resection remains the only hope for cure of CRLM...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28806726/replication-fork-slowing-and-stalling-are-distinct-checkpoint-independent-consequences-of-replicating-damaged-dna
#19
Divya Ramalingam Iyer, Nicholas Rhind
In response to DNA damage during S phase, cells slow DNA replication. This slowing is orchestrated by the intra-S checkpoint and involves inhibition of origin firing and reduction of replication fork speed. Slowing of replication allows for tolerance of DNA damage and suppresses genomic instability. Although the mechanisms of origin inhibition by the intra-S checkpoint are understood, major questions remain about how the checkpoint regulates replication forks: Does the checkpoint regulate the rate of fork progression? Does the checkpoint affect all forks, or only those encountering damage? Does the checkpoint facilitate the replication of polymerase-blocking lesions? To address these questions, we have analyzed the checkpoint in the fission yeast Schizosaccharomyces pombe using a single-molecule DNA combing assay, which allows us to unambiguously separate the contribution of origin and fork regulation towards replication slowing, and allows us to investigate the behavior of individual forks...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28803425/frameshift-mutations-in-repeat-sequences-of-ank3-hacd4-tcp10l-tp53bp1-mfn1-lcmt2-rnmt-trmt6-mettl8-and-mettl16-genes-in-colon-cancers
#20
Su Yeon Yeon, Yun Sol Jo, Eun Ji Choi, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee
Diminished ANK3 contributes to cell survival by inhibiting detachment-induced apoptosis. TP53BP1 that interacts with p53 and MFN1 that encodes a mitochondrial membrane protein are considered to have tumor suppressor gene (TSG) functions. HACD4 involving fatty acid synthesis and TCPL10 with transcription regulation functions are considered TSGs. Many genes involved in DNA methylations such as LCMT2, RNMT, TRMT6, METTL8 and METTL16 are often perturbed in cancer. The aim of our study was to find whether these genes were mutated in colorectal cancer (CRC)...
August 12, 2017: Pathology Oncology Research: POR
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