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https://www.readbyqxmd.com/read/29320491/cdc73-suppresses-genome-instability-by-mediating-telomere-homeostasis
#1
Rahul V Nene, Christopher D Putnam, Bin-Zhong Li, Katarina G Nguyen, Anjana Srivatsan, Christopher S Campbell, Arshad Desai, Richard D Kolodner
Defects in the genes encoding the Paf1 complex can cause increased genome instability. Loss of Paf1, Cdc73, and, Ctr9, but not Rtf1 or Leo1, caused increased accumulation of gross chromosomal rearrangements (GCRs). Combining the cdc73Δ mutation with individual deletions of 43 other genes, including TEL1 and YKU80, which are involved in telomere maintenance, resulted in synergistic increases in GCR rates. Whole genome sequence analysis of GCRs indicated that there were reduced relative rates of GCRs mediated by de novo telomere additions and increased rates of translocations and inverted duplications in cdc73Δ single and double mutants...
January 10, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29310692/epigenetic-supersimilarity-of-monozygotic-twin-pairs
#2
Timothy E Van Baak, Cristian Coarfa, Pierre-Antoine Dugué, Giovanni Fiorito, Eleonora Laritsky, Maria S Baker, Noah J Kessler, Jianrong Dong, Jack D Duryea, Matt J Silver, Ayden Saffari, Andrew M Prentice, Sophie E Moore, Akram Ghantous, Michael N Routledge, Yun Yun Gong, Zdenko Herceg, Paolo Vineis, Gianluca Severi, John L Hopper, Melissa C Southey, Graham G Giles, Roger L Milne, Robert A Waterland
BACKGROUND: Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities of monozygotic twins have been assumed to be largely due to their genetic identity. RESULTS: Here, by analyzing data from a genome-scale study of DNA methylation in monozygotic and dizygotic twins, we identified genomic regions at which the epigenetic similarity of monozygotic twins is substantially greater than can be explained by their genetic identity...
January 9, 2018: Genome Biology
https://www.readbyqxmd.com/read/29290466/structural-insights-into-yeast-telomerase-recruitment-to-telomeres
#3
Hongwen Chen, Jing Xue, Dmitri Churikov, Evan P Hass, Shaohua Shi, Laramie D Lemon, Pierre Luciano, Alison A Bertuch, David C Zappulla, Vincent Géli, Jian Wu, Ming Lei
Telomerase maintains chromosome ends from humans to yeasts. Recruitment of yeast telomerase to telomeres occurs through its Ku and Est1 subunits via independent interactions with telomerase RNA (TLC1) and telomeric proteins Sir4 and Cdc13, respectively. However, the structures of the molecules comprising these telomerase-recruiting pathways remain unknown. Here, we report crystal structures of the Ku heterodimer and Est1 complexed with their key binding partners. Two major findings are as follows: (1) Ku specifically binds to telomerase RNA in a distinct, yet related, manner to how it binds DNA; and (2) Est1 employs two separate pockets to bind distinct motifs of Cdc13...
December 27, 2017: Cell
https://www.readbyqxmd.com/read/29288197/recruitment-and-allosteric-stimulation-of-a-histone-deubiquitinating-enzyme-during-heterochromatin-assembly
#4
Alexis Zukowksi, Nouf Omar Al-Afaleq, Emily D Duncan, Tingting Yao, Aaron M Johnson
Heterochromatin formation in budding yeast is regulated by the silent information regulator (SIR) complex. The SIR complex comprises the NAD-dependent deacetylase Sir2, the scaffolding protein Sir4, and the nucleosome-binding protein Sir3. Transcriptionally active regions present a challenge to SIR complex-mediated de novo heterochromatic silencing due to the presence of antagonistic histone PTMs, including acetylation and methylation. Methylation of histone H3K4 and H3K79 are dependent on mono-ubiquitination of histone H2B (H2B-Ub)...
December 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29286521/impact-of-chronic-blood-viral-infection-on-lymphocyte-telomere-length-in-chornobyl-clean-up-workers-in-a-remote-period-after-radiation-exposure
#5
I M Ilienko, O V Lyaskivska, O A Belayev, O Y Pleskach, V I Shinkarenko, D A Bazyka
OBJECTIVE: To assess whether telomere length in lymphocytes of Chornobyl clean up workers at a late period 30 years after the exposure to ionizing radiation is influenced by a chronic blood viral infection and to determine role of viral carriage in cellular senescence. PATIENTS AND METHODS: Study group included 70 Chornobyl cleanup male workers 30 years after exposure {doses of external exposure (602.67 ± 114.19) mSv (M ± m); age (59.75 ± 0.82) yrs}. Relative telomere length (RTL) was analysed by fluorescence in situ hybridization and flow cytometry, immune cell subsets by standard combinations of monoclonal antibodies (CD45/14, CD3/19, CD4/8, CD3/HLADR, CD3/16/56, TCRγδ) and flow cytometry; antiviral immunity was performed determining the chronic phase antibodies to viruses: Hepatitis C (HCV), Cytomegalovirus (CMV), Toxoplasma gondii (TOX), Herpes simplex (HSV) and Epstein Barr virus (EBV VCA IgG and EBV NA IgG)...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/29274177/links-between-parental-life-histories-of-wild-salmon-and-the-telomere-lengths-of-their-offspring
#6
D McLennan, J D Armstrong, D C Stewart, S Mckelvey, W Boner, P Monaghan, N B Metcalfe
The importance of parental contributions to offspring development and subsequent performance is self-evident at a genomic level; however, parents can also affect offspring fitness by indirect genetic and environmental routes. The life history strategy that an individual adopts will be influenced by both genes and environment; and this may have important consequences for offspring. Recent research has linked telomere dynamics (i.e. telomere length and loss) in early life to future viability and longevity. Moreover, a number of studies have reported a heritable component to telomere length across a range of vertebrates, though the effects of other parental contribution pathways have been far less studied...
December 23, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/29259092/effects-of-temperature-on-the-meiotic-recombination-landscape-of-the-yeast-saccharomyces-cerevisiae
#7
Ke Zhang, Xue-Chang Wu, Dao-Qiong Zheng, Thomas D Petes
Although meiosis in warm-blooded organisms takes place in a narrow temperature range, meiosis in many organisms occurs over a wide variety of temperatures. We analyzed the properties of meiosis in the yeast Saccharomyces cerevisiae in cells sporulated at 14°C, 30°C, or 37°C. Using comparative-genomic-hybridization microarrays, we examined the distribution of Spo11-generated meiosis-specific double-stranded DNA breaks throughout the genome. Although there were between 300 and 400 regions of the genome with high levels of recombination (hot spots) observed at each temperature, only about 20% of these hot spots were found to have occurred independently of the temperature...
December 19, 2017: MBio
https://www.readbyqxmd.com/read/29242238/short-leukocyte-telomere-length-precedes-clinical-expression-of-atherosclerosis-blood-and-muscle-model
#8
Athanase Benetos, Simon Toupance, Sylvie Gautier, Carlos Labat, Masayuki Kimura, Pascal M Rossi, Nicla Settembre, Jacques Hubert, Luc Frimat, Baptiste Bertrand, Mourad Boufi, Xavier Flecher, Nicolas Sadoul, Pascal Eschwege, Michà le Kessler, Irene P Tzanetakou, Ilias P Doulamis, Panagiotis S Konstantopoulos, Aspasia I Tzani, Laskarina-Maria Korou, Anastasios Gkogkos, Konstantinos G Perreas, Evangelos Menenakos, George Samanidis, Michail Vasiloglou-Gkanis, Jeremy D Kark, Sergueï Malikov, Simon Verhulst, Abraham Aviv
Rationale:  Short telomere length (TL) in leukocytes is associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown whether this relationship stems from having inherently short leukocyte TL (LTL) at birth and/or a faster LTL attrition thereafter. LTL represents TL in the highly proliferative hematopoietic system, while TL in skeletal muscle (M) represents a minimally replicative tissue. Objective: We measured LTL and MTL in the same individuals with a view to obtain comparative metrics for lifelong LTL attrition and learn about the temporal association of LTL with ASCVD...
December 14, 2017: Circulation Research
https://www.readbyqxmd.com/read/29233913/reference-quality-genome-assemblies-of-three-parastagonospora-nodorum%C3%A2-isolates-differing-in-virulence-on-wheat
#9
Jonathan K Richards, Nathan A Wyatt, Zhaohui Liu, Justin D Faris, Timothy L Friesen
Parastagonospora nodorum, the causal agent of Septoria nodorum blotch of wheat, has emerged as a model necrotrophic fungal organism for the study of host-microbe interactions. To date, three necrotrophic effectors have been identified and characterized from this pathogen, including SnToxA, SnTox1, and SnTox3. Necrotrophic effector identification was greatly aided by the development of a draft genome of Australian isolate SN15 via Sanger sequencing, yet remained largely fragmented. This research presents the development of near-finished genomes of P...
December 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29230030/silica-inhalation-altered-telomere-length-and-gene-expression-of-telomere-regulatory-proteins-in-lung-tissue-of-rats
#10
Mohammad Shoeb, Pius Joseph, Vamsi Kodali, Gul Mustafa, Breanne Y Farris, Christina Umbright, Jenny R Roberts, Aaron Erdely, James M Antonini
Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229970/regression-to-the-mean-apparent-data-errors-and-biologically-extraordinary-results-letter-regarding-changes-in-telomere-length-3-5-years-after-gastric-bypass-surgery
#11
D L Smith, D M Thomas, C O Siu, S Verhulst, D B Allison
International Journal of Obesity accepted article preview online, 12 December 2017. doi:10.1038/ijo.2017.298.
December 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29223973/chromosomal-rearrangements-in-the-11p15-imprinted-region-17-new-11p15-5-duplications-with-associated-phenotypes-and-putative-functional-consequences
#12
Solveig Heide, Sandra Chantot-Bastaraud, Boris Keren, Madeleine D Harbison, Salah Azzi, Sylvie Rossignol, Caroline Michot, Marilyn Lackmy-Port Lys, Bénédicte Demeer, Claudine Heinrichs, Ron S Newfield, Pierre Sarda, Lionel Van Maldergem, Véronique Trifard, Eloise Giabicani, Jean-Pierre Siffroi, Yves Le Bouc, Irène Netchine, Frédéric Brioude
BACKGROUND: The 11p15 region contains two clusters of imprinted genes. Opposite genetic and epigenetic anomalies of this region result in two distinct growth disturbance syndromes: Beckwith-Wiedemann (BWS) and Silver-Russell syndromes (SRS). Cytogenetic rearrangements within this region represent less than 3% of SRS and BWS cases. Among these, 11p15 duplications were infrequently reported and interpretation of their pathogenic effects is complex. OBJECTIVES: To report cytogenetic and methylation analyses in a cohort of patients with SRS/BWS carrying 11p15 duplications and establish genotype/phenotype correlations...
December 9, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29191871/mr-imaging-characteristics-associate-with-tumor-associated-macrophages-in-glioblastoma-and-provide-an-improved-signature-for-survival-prognostication
#13
J Zhou, M V Reddy, B K J Wilson, D A Blair, A Taha, C M Frampton, R A Eiholzer, P Y C Gan, F Ziad, Z Thotathil, S Kirs, N A Hung, J A Royds, T L Slatter
BACKGROUND AND PURPOSE: In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determined whether routine MR imaging features could predict molecular subtypes of glioblastoma that differ in the content of tumor-associated macrophages. MATERIALS AND METHODS: Seven internally derived MR imaging features were assessed in 180 patients, and 25 features from the Visually AcceSAble Rembrandt Images feature set were assessed in 164 patients...
November 30, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29169922/site-specific-transfer-of-chromosomal-segments-and-genes-in-wheat-engineered-chromosomes
#14
Jing Yuan, Qinghua Shi, Xiang Guo, Yalin Liu, Handong Su, Xianrui Guo, Zhenling Lv, Fangpu Han
Recently, engineered minichromosomes have been produced using a telomere-mediated truncation technique in some plants. However, the study on transferring genes to minichromosomes is very limited. Here, telomere-mediated truncation was successfully performed in common wheat (Triticum aestivum) to generate stable truncated chromosomes accompanied by a relatively high frequency of chromosomal rearrangements. After the cross between transgenic parents, a promoter-less DsRed gene in a chromosome from one parent was transferred to another chromosome from the other parent at the site behind a maize ubiquitin promoter via the Cre/lox system...
November 13, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/29161777/structure-based-design-and-evaluation-of-synthetic-porphyrin-derivatives-as-g-quadruplex-stabilizing-anticancer-agents
#15
R N Bhadane, D B Meshram, R M Gilhotra
G-quadruplex structures formed in telomeres and proto-oncogene represent a potentially useful target for anticancer drugs. Stabilization of this arrangement may inhibit the further action of different enzymes involved in cancer cell immortalization. In present work structure based drug design and synthesis was carried out on series of meso-substituted porphyrin analogues. The interaction of porphyrin derivatives with G-quadruplex DNA has been explored by virtual screening procedure. Some of the potential binding agents were then synthesized and evaluated in-vitro by MTT and PCR stop assay...
November 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/29161754/the-sorghum-bicolor-reference-genome-improved-assembly-gene-annotations-a-transcriptome-atlas-and-signatures-of-genome-organization
#16
Ryan F McCormick, Sandra K Truong, Avinash Sreedasyam, Jerry Jenkins, Shengqiang Shu, David Sims, Megan Kennedy, Mojgan Amirebrahimi, Brock D Weers, Brian McKinley, Ashley Mattison, Daryl T Morishige, Jane Grimwood, Jeremy Schmutz, John E Mullet
Sorghum bicolor is a drought tolerant C4 grass used for production of grain, forage, sugar, and lignocellulosic biomass and a genetic model for C4 grasses due to its relatively small genome (~800 Mbp), diploid genetics, diverse germplasm, and colinearity with other C4 grass genomes. In this study, deep sequencing, genetic linkage analysis, and transcriptome data were used to produce and annotate a high-quality reference genome sequence. Reference genome sequence order was improved, 29.6 Mbp of additional sequence was incorporated, the number of genes annotated increased 24% to 34,211, average gene length and N50 increased, and error frequency was reduced 10-fold to 1 per 100 kbp...
November 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29152572/a-null-mutation-in-serpine1-protects-against-biological-aging-in-humans
#17
Sadiya S Khan, Sanjiv J Shah, Ekaterina Klyachko, Abigail S Baldridge, Mesut Eren, Aaron T Place, Abraham Aviv, Eli Puterman, Donald M Lloyd-Jones, Meadow Heiman, Toshio Miyata, Sweta Gupta, Amy D Shapiro, Douglas E Vaughan
Plasminogen activator inhibitor-1 (PAI-1) has been shown to be a key component of the senescence-related secretome and a direct mediator of cellular senescence. In murine models of accelerated aging, genetic deficiency and targeted inhibition of PAI-1 protect against aging-like pathology and prolong life span. However, the role of PAI-1 in human longevity remains unclear. We hypothesized that a rare loss-of-function mutation in SERPINE1 (c.699_700dupTA), which encodes PAI-1, could play a role in longevity and metabolism in humans...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29150481/identification-of-pleiotropic-cancer-susceptibility-variants-from-genome-wide-association-studies-reveals-functional-characteristics
#18
Yi-Hsuan Wu, Rebecca E Graff, Michael N Passarelli, Joshua D Hoffman, Elad Ziv, Thomas J Hoffmann, John S Witte
BACKGROUND: There exists compelling evidence that some genetic variants are associated with the risk of multiple cancer sites (i.e., pleiotropy). However, the biological mechanisms through which the pleiotropic variants operate are unclear. METHODS: We obtained all cancer risk associations from the National Human Genome Research Institute-European Bioinformatics Institute GWAS Catalog, and correlated cancer risk variants were clustered into groups. Pleiotropic variant groups and genes were functionally annotated...
November 17, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#19
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29138179/association-between-leukocyte-telomere-length-and-the-risk-of-incident-atrial-fibrillation-the-framingham-heart-study
#20
Laila Staerk, Biqi Wang, Kathryn L Lunetta, Robert H Helm, Darae Ko, Jason A Sherer, Patrick T Ellinor, Steven A Lubitz, David D McManus, Ramachandran S Vasan, Emelia J Benjamin, Ludovic Trinquart
BACKGROUND: Advancing age is a prominent risk factor for atrial fibrillation (AF). Shorter telomere length is a biomarker of biological aging, but the link between shorter telomere length and increased risk of AF remains unclear. We examined the association between shorter leukocyte telomere length (LTL) and incident AF. METHODS AND RESULTS: We included AF-free participants from the observational Framingham Heart Study Offspring cohort from 1995 to 1998, who had LTL measurements...
November 14, 2017: Journal of the American Heart Association
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