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Genomic stability

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https://www.readbyqxmd.com/read/29053959/restoration-of-replication-fork-stability-in-brca1-and-brca2-deficient-cells-by-inactivation-of-snf2-family-fork-remodelers
#1
Angelo Taglialatela, Silvia Alvarez, Giuseppe Leuzzi, Vincenzo Sannino, Lepakshi Ranjha, Jen-Wei Huang, Chioma Madubata, Roopesh Anand, Brynn Levy, Raul Rabadan, Petr Cejka, Vincenzo Costanzo, Alberto Ciccia
To ensure the completion of DNA replication and maintenance of genome integrity, DNA repair factors protect stalled replication forks upon replication stress. Previous studies have identified a critical role for the tumor suppressors BRCA1 and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease after replication stress. Here we show that depletion of SMARCAL1, a SNF2-family DNA translocase that remodels stalled forks, restores replication fork stability and reduces the formation of replication stress-induced DNA breaks and chromosomal aberrations in BRCA1/2-deficient cells...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29052136/human-t-cell-leukemia-virus-type-1-infection-and-adult-t-cell-leukemia
#2
Chi-Ping Chan, Kin-Hang Kok, Dong-Yan Jin
Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus discovered to cause adult T-cell leukemia (ATL), a highly aggressive blood cancer. HTLV-1 research in the past 35 years has been most revealing in the mechanisms of viral oncogenesis. HTLV-1 establishes a lifelong persistent infection in CD4(+) T lymphocytes. The infection outcome is governed by host immunity. ATL develops in 2-5% of infected individuals 30-50 years after initial exposure. HTLV-1 encodes two oncoproteins Tax and HBZ, which are required for initiation of cellular transformation and maintenance of cell proliferation, respectively...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29050555/natural-variation-in-human-clocks
#3
Malcolm von Schantz
Our own species has a diurnal activity pattern and an average circadian period of 24.2h. Exact determination of circadian period requires expensive and intrusive protocols, and investigators are therefore using chronotype questionnaires as a proxy quantitative measure. Both measures show a normal distribution suggestive of a polygenic trait. The genetic components of the 24-h feedback loop that generates circadian rhythms within our cells have been mapped in detail, identifying a number of candidate genes which have been investigated for genetic polymorphisms relating to the phenotypic variance...
2017: Advances in Genetics
https://www.readbyqxmd.com/read/29048940/a-cpgcluster-teaching-learning-based-optimization-for-prediction-of-cpg-islands-in-the-human-genome
#4
Cheng-Hong Yang, Yi-Cheng Chiang, Li-Yeh Chuang, Yu-Da Lin
Many CpG island detection methods have been proposed based on sliding window and clustering technology, but the accuracy of these methods is proportional to the time required. Therefore, an accurate and rapid method for identifying CpG islands remains an important challenge in the complete human genome. We propose a hybrid method CpGTLBO to detect the CpG islands in the human genome. The method uses the clustering approach and the teaching-learning-based optimization (TLBO) algorithm. The clustering approach is used to detect CpG island candidates, and it can effectively reduce the huge volume of unnecessary DNA fragments...
October 19, 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/29047390/roles-of-bccip-deficiency-in-mammary-tumorigenesis
#5
Roberto Droz-Rosario, Huimei Lu, Jingmei Liu, Ning-Ang Liu, Shridar Ganesan, Bing Xia, Bruce G Haffty, Zhiyuan Shen
BACKGROUND: Dysregulated DNA repair and cell proliferation controls are essential driving forces in mammary tumorigenesis. BCCIP was originally identified as a BRCA2 and CDKN1A interacting protein that has been implicated in maintenance of genomic stability, cell cycle regulation, and microtubule dynamics. The aims of this study were to determine whether BCCIP deficiency contributes to mammary tumorigenesis, especially for a subset of breast cancers with 53BP1 abnormality, and to reveal the mechanistic implications of BCCIP in breast cancer interventions...
October 18, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29046436/caenorhabditis-elegans-bub-3-and-san-1-mad3-spindle-assembly-checkpoint-components-are-required-for-genome-stability-in-response-to-treatment-with-ionizing-radiation
#6
Simone Bertolini, Bin Wang, Bettina Meier, Ye Hong, Anton Gartner
Relatively little is known about the crosstalk between the spindle assembly checkpoint and the DNA damage response, especially in multicellular organisms. We performed a Caenorhabditis elegans forward genetic screen to uncover new genes involved in the repair of DNA damage induced by ionizing radiation. We isolated a mutation, gt2000 which confers hypersensitivity to ionizing radiation and showed that gt2000 introduces a premature stop in bub-3 BUB-3 is a key component of the spindle assembly checkpoint. We provide evidence that BUB-3 acts during development and in the germline; irradiated bub-3(gt2000) larvae are developmentally retarded and form abnormal vulvae...
October 18, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29045827/yeast-srs2-helicase-promotes-redistribution-of-single-stranded-dna-bound-rpa-and-rad52-in-homologous-recombination-regulation
#7
Luisina De Tullio, Kyle Kaniecki, Youngho Kwon, J Brooks Crickard, Patrick Sung, Eric C Greene
Srs2 is a super-family 1 helicase that promotes genome stability by dismantling toxic DNA recombination intermediates. However, the mechanisms by which Srs2 remodels or resolves recombination intermediates remain poorly understood. Here, single-molecule imaging is used to visualize Srs2 in real time as it acts on single-stranded DNA (ssDNA) bound by protein factors that function in recombination. We demonstrate that Srs2 is highly processive and translocates rapidly (∼170 nt per second) in the 3'→5' direction along ssDNA saturated with replication protein A (RPA)...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29044712/inferring-the-geographic-origin-of-a-range-expansion-latitudinal-and-longitudinal-coordinates-inferred-from-genomic-data-in-an-abc-framework-with-the-program-x-origin
#8
Qixin He, Joyce R Prado, L Lacey Knowles
Climatic or environmental change is not only driving distributional shifts in species today, but it has also caused distributions to expand and contract in the past. Inferences about the geographic locations of past populations, especially regions that served as refugia (i.e., source populations) and migratory routes are a challenging endeavor. Refugial areas may be evidenced from fossil records or regions of temporal stability inferred from ecological niche models. Genomic data offer an alternative and broadly applicable source of information about the locality of refugial areas, especially relative to fossil data, which are either unavailable or incomplete for most species...
October 16, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/29043646/long-term-imaging-of-dna-damage-and-cell-cycle-progression-in-budding-yeast-using-spinning-disk-confocal-microscopy
#9
Riccardo Montecchi, Etienne Schwob
Live cell imaging can monitor biological processes in time and space by providing quantitative measurements of cell behavior on a single-cell basis and in live conditions. However the illumination required to visualize fluorescently tagged endogenous proteins often perturbs cellular physiology, a problem particularly acute for yeast cells that are small, highly photosensitive and with scarce protein content. Analyzing the activation of the DNA damage response (DDR) in various yeast mutants or growth conditions, as well as its consequences for cell cycle progression and cell viability over extended periods of time therefore requires a special microscopy setup that does not by itself create DNA damage or perturb cell growth...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043643/imaging-of-dna-ultrafine-bridges-in-budding-yeast
#10
Oliver Quevedo, Michael Lisby
DNA ultrafine bridges (UFBs) are a type of chromatin-free DNA bridges that connect sister chromatids in anaphase and pose a threat to genome stability. However, little is known about the origin of these structures, and how they are sensed and resolved by the cell. In this chapter, we review tools and methods for studying UFBs by fluorescence microscopy including chemical and genetic approaches to induce UFBs in the model organism Saccharomyces cerevisiae.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043630/dynamic-architecture-of-eukaryotic-dna-replication-forks-in-vivo-visualized-by-electron-microscopy
#11
Ralph Zellweger, Massimo Lopes
The DNA replication process can be heavily perturbed by several different conditions of genotoxic stress, particularly relevant for cancer onset and therapy. The combination of psoralen crosslinking and electron microscopy has proven instrumental to reveal the fine architecture of in vivo DNA replication intermediates and to uncover their remodeling upon specific conditions of genotoxic stress. The replication structures are stabilized in vivo (by psoralen crosslinking) prior to extraction and enrichment procedures, allowing their visualization at the transmission electron microscope...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043625/genome-wide-profiling-of-dna-double-strand-breaks-by-the-bless-and-bliss-methods
#12
Reza Mirzazadeh, Tomasz Kallas, Magda Bienko, Nicola Crosetto
DNA double-strand breaks (DSBs) are major DNA lesions that are constantly formed during physiological processes such as DNA replication, transcription, and recombination, or as a result of exogenous agents such as ionizing radiation, radiomimetic drugs, and genome editing nucleases. Unrepaired DSBs threaten genomic stability by leading to the formation of potentially oncogenic rearrangements such as translocations. In past few years, several methods based on next-generation sequencing (NGS) have been developed to study the genome-wide distribution of DSBs or their conversion to translocation events...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043618/integrated-microarray-based-tools-for-detection-of-genomic-dna-damage-and-repair-mechanisms
#13
Patrick van Eijk, Yumin Teng, Mark R Bennet, Katie E Evans, James R Powell, Richard M Webster, Simon H Reed
The genetic information contained within the DNA molecule is highly susceptible to chemical and physical insult, caused by both endogenous and exogenous sources that can generate in the order of thousands of lesions a day in each of our cells (Lindahl, Nature 362(6422):709-715, 1993). DNA damages interfere with DNA metabolic processes such as transcription and replication and can be potent inhibitors of cell division and gene expression. To combat these regular threats to genome stability, a host of DNA repair mechanisms have evolved...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043612/the-a-like-faker-assay-for-measuring-yeast-chromosome-iii-stability
#14
Carolina A Novoa, J Sidney Ang, Peter C Stirling
The ability to rapidly assess chromosome instability (CIN) has enabled profiling of most yeast genes for potential effects on genome stability. The A-like faker (ALF) assay is one of several qualitative and quantitative marker loss assays that indirectly measure loss or conversion of genetic material using a counterselection step. The ALF assay relies on the ability to count spurious mating events that occur upon loss of the MATα locus of haploid Saccharomyces cerevisiae strains. Here, we describe the deployment of the ALF assay for both rapid and simple qualitative, and more in-depth quantitative analysis allowing determination of absolute ALF frequencies...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043077/recent-advances-in-understanding-werner-syndrome
#15
REVIEW
Raghavendra A Shamanna, Deborah L Croteau, Jong-Hyuk Lee, Vilhelm A Bohr
Aging, the universal phenomenon, affects human health and is the primary risk factor for major disease pathologies. Progeroid diseases, which mimic aging at an accelerated rate, have provided cues in understanding the hallmarks of aging. Mutations in DNA repair genes as well as in telomerase subunits are known to cause progeroid syndromes. Werner syndrome (WS), which is characterized by accelerated aging, is an autosomal-recessive genetic disorder. Hallmarks that define the aging process include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication...
2017: F1000Research
https://www.readbyqxmd.com/read/29042795/significant-association-of-the-exo1-rs851797-polymorphism-with-clinical-outcome-of-ovarian-cancer
#16
Tingyan Shi, Rong Jiang, Pan Wang, Yuan Xu, Sheng Yin, Xi Cheng, Rongyu Zang
BACKGROUND: Exonuclease 1 (EXO1), one of DNA mismatch repair pathway genes, functions in maintaining genomic stability and affects tumor progression. We hypothesized that genetic variations in EXO1 may predict clinical outcomes in epithelial ovarian cancer (EOC). METHODS: In this cohort study with 1,030 consecutive EOC patients, we genotyped four potentially functional polymorphisms in EXO1 by the Taqman assay and evaluated their associations with patients' survival...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29042561/aunip-c1orf135-directs-dna-double-strand-breaks-towards-the-homologous-recombination-repair-pathway
#17
Jiangman Lou, Hongxia Chen, Jinhua Han, Hanqing He, Michael S Y Huen, Xin-Hua Feng, Ting Liu, Jun Huang
DNA double-strand breaks (DSBs) are mainly repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ). Here, we identify AUNIP/C1orf135, a largely uncharacterized protein, as a key determinant of DSB repair pathway choice. AUNIP physically interacts with CtIP and is required for efficient CtIP accumulation at DSBs. AUNIP possesses intrinsic DNA-binding ability with a strong preference for DNA substrates that mimic structures generated at stalled replication forks. This ability to bind DNA is necessary for the recruitment of AUNIP and its binding partner CtIP to DSBs, which in turn drives CtIP-dependent DNA-end resection and HR repair...
October 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29042409/recq-like-helicases-sgs1-and-blm-regulate-r-loop-associated-genome-instability
#18
Emily Yun-Chia Chang, Carolina A Novoa, Maria J Aristizabal, Yan Coulombe, Romulo Segovia, Richa Chaturvedi, Yaoqing Shen, Christelle Keong, Annie S Tam, Steven J M Jones, Jean-Yves Masson, Michael S Kobor, Peter C Stirling
Sgs1, the orthologue of human Bloom's syndrome helicase BLM, is a yeast DNA helicase functioning in DNA replication and repair. We show that SGS1 loss increases R-loop accumulation and sensitizes cells to transcription-replication collisions. Yeast lacking SGS1 accumulate R-loops and γ-H2A at sites of Sgs1 binding, replication pausing regions, and long genes. The mutation signature of sgs1Δ reveals copy number changes flanked by repetitive regions with high R-loop-forming potential. Analysis of BLM in Bloom's syndrome fibroblasts or by depletion of BLM from human cancer cells confirms a role for Sgs1/BLM in suppressing R-loop-associated genome instability across species...
October 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29042072/mir-200b-downregulates-kruppel-like-factor-2-klf2-during-acute-hypoxia-in-human-endothelial-cells
#19
Rafal Bartoszewski, Marcin Serocki, Anna Janaszak-Jasiecka, Sylwia Bartoszewska, Kinga Kochan-Jamrozy, Arkadiusz Piotrowski, Jarosław Króliczewski, James F Collawn
The role of microRNAs in controlling angiogenesis is recognized as a promising therapeutic target in both cancer and cardiovascular disorders. However, understanding a miRNA's pleiotropic effects on angiogenesis is a limiting factor for these types of therapeutic approaches. Using genome-wide next-generation sequencing, we examined the role of an antiangiogenic miRNA, miR-200b, in primary human endothelial cells. The results indicate that miR-200b has complex effects on hypoxia-induced angiogenesis in human endothelia and importantly, that many of the reported miR-200b effects using miRNA overexpression may not be representative of the physiological role of this miRNA...
October 13, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29040774/assessing-the-between-background-stability-of-metabolic-effects-arising-from-lignin-related-transgenic-modifications-in-two-populus-hybrids-using-non-targeted-metabolomics
#20
Andrew R Robinson, Rebecca Dauwe, Shawn D Mansfield
The advances in 'high-throughput' biology have significantly expanded our fundamental understanding of complex biological processes inherent to tree growth and development. Relative to the significant achievements attained with whole genome re-sequencing and transcriptomics efforts, the development and power of post-transcriptional tools such as proteomics and metabolomics continue to lag behind in tree biology. However, the inclusion of these powerful functional genomics platforms should substantially enable systems biology assessments of tree development, physiology and response(s) to biotic and abiotic stresses...
October 10, 2017: Tree Physiology
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