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alternative lengthening of telomeres

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https://www.readbyqxmd.com/read/28425984/withaferin-a-kills-cancer-cells-with-and-without-telomerase-chemical-computational-and-experimental-evidences
#1
Yue Yu, Shashank P Katiyar, Durai Sundar, Zeenia Kaul, Eijiro Miyako, Zhenya Zhang, Sunil C Kaul, Roger R Reddel, Renu Wadhwa
Maintenance of telomere length is the most consistent attribute of cancer cells. Tightly connected to their capacity to overcome replicative mortality, it is achieved either by activation of telomerase or an Alternative mechanism of Lengthening of Telomeres (ALT). Disruption of either of these mechanisms has been shown to induce DNA damage signalling leading to senescence or apoptosis. Telomerase inhibitors are considered as potential anticancer drugs but are ineffective for ALT cancers (~15% of all cancers)...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28412741/opposite-effects-of-gcn5-and-pcaf-knockdowns-on-the-alternative-mechanism-of-telomere-maintenance
#2
Maya Jeitany, Dalal Bakhos-Douaihy, David C Silvestre, Jose R Pineda, Nicolas Ugolin, Angela Moussa, Laurent R Gauthier, Didier Busso, Marie-Pierre Junier, Hervé Chneiweiss, Sylvie Chevillard, Chantal Desmaze, François D Boussin
Cancer cells can use a telomerase-independent mechanism, known as alternative lengthening of telomeres (ALT), to elongate their telomeres. General control non-derepressible 5 (GCN5) and P300/CBP-associated factor (PCAF) are two homologous acetyltransferases that are mutually exclusive subunits in SAGA-like complexes. Here, we reveal that down regulation of GCN5 and PCAF had differential effects on some phenotypic characteristics of ALT cells. Our results suggest that GCN5 is present at telomeres and opposes telomere recombination, in contrast to PCAF that may indirectly favour them in ALT cells...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398700/differential-requirements-for-dna-repair-proteins-in-immortalized-cell-lines-using-alternative-lengthening-of-telomere-mechanisms
#3
Alaina R Martinez, Zeenia Kaul, Jeffrey D Parvin, Joanna Groden
Cancer cells require telomere maintenance to enable uncontrolled growth. Most often telomerase is activated, although a subset of human cancers are telomerase-negative and depend on recombination-based mechanisms known as ALT (Alternative Lengthening of Telomeres). ALT depends on proteins that are essential for homologous recombination, including BLM and the MRN complex, to extend telomeres. This study surveyed the requirement for requisite homologous recombination proteins, yet to be studied in human ALT cell lines, by protein depletion using RNA interference...
April 11, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28371511/alternative-lengthening-of-telomeres-and-atrx-daxx-loss-can-be-reliably-detected-in-fnas-of-pancreatic-neuroendocrine-tumors
#4
Christopher J VandenBussche, Derek B Allison, Mindy K Graham, Vivek Charu, Anne Marie Lennon, Christopher L Wolfgang, Ralph H Hruban, Christopher M Heaphy
BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) frequently use the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. ALT is strongly correlated with α thalassemia-mental retardation, X linked (ATRX), and death domain-associated protein 6 (DAXX) alterations and a poor prognosis in patients with primary PanNET. Because fine-needle aspiration (FNA) is a noninvasive way to sample tumors, the authors evaluated whether they could accurately detect ALT and loss of ATRX/DAXX in a primary PanNET cohort of FNAs...
April 3, 2017: Cancer
https://www.readbyqxmd.com/read/28366536/the-human-ctc1-stn1-ten1-complex-regulates-telomere-maintenance-in-alt-cancer-cells
#5
Chenhui Huang, Pingping Jia, Megan Chastain, Olga Shiva, Weihang Chai
Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle...
March 30, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28265354/genistein-suppresses-the-proliferation-of-telomerase-negative-cells
#6
Chuan-Chuan Lin, Meng-Hsun Hsieh, Shu-Chun Teng
In both tumor and yeast cells that lack telomerase, telomeres are maintained via an alternative recombination mechanism. In this study, we tested genistein, a potential TOP2 inhibitor required for telomere-telomere recombination, on the repression of telomere-telomere recombination. Genistein on the repression of type II recombination on a tlc1 yeast strain was examined by the telomeric DNA structures using Southern blot analysis. Telomere patterns of freshly dissected tlc1 spores containing an empty plasmid (pYES2) or a yeast TOP2 (yTOP2) plasmid were analyzed...
March 2017: Food Science & Nutrition
https://www.readbyqxmd.com/read/28240303/transient-alt-activation-protects-human-primary-cells-from-chromosome-instability-induced-by-low-chronic-oxidative-stress
#7
Elisa Coluzzi, Rossella Buonsante, Stefano Leone, Anthony J Asmar, Kelley L Miller, Daniela Cimini, Antonella Sgura
Cells are often subjected to the effect of reactive oxygen species (ROS) as a result of both intracellular metabolism and exposure to exogenous factors. ROS-dependent oxidative stress can induce 8-oxodG within the GGG triplet found in the G-rich human telomeric sequence (TTAGGG), making telomeres highly susceptible to ROS-induced oxidative damage. Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes and their dysfunction is believed to affect a wide range of cellular and/or organismal processes...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195879/fibrin-associated-ebv-positive-large-b-cell-lymphoma-an-indolent-neoplasm-with-features-distinct-from-diffuse-large-b-cell-lymphoma-associated-with-chronic-inflammation
#8
Daniel F Boyer, Penelope A McKelvie, Laurence de Leval, Kerstin L Edlefsen, Young-Hyeh Ko, Zachary A Aberman, Alexandra E Kovach, Aneal Masih, Ha T Nishino, Lawrence M Weiss, Alan K Meeker, Valentina Nardi, Maryknoll Palisoc, Lina Shao, Stefania Pittaluga, Judith A Ferry, Nancy Lee Harris, Aliyah R Sohani
Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.5 years with a M:F ratio of 3. In all 12 cases, the lymphoma was an incidental microscopic finding involving atrial myxomas (n=3), thrombi associated with endovascular grafts (n=3), chronic hematomas (n=2), and pseudocysts (n=4)...
March 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28152565/sphere-induced-rejuvenation-of-swine-and-human-m%C3%A3-ller-glia-is-primarily-caused-by-telomere-elongation
#9
Ni Xu, Yao Chen, Kevin C Dean, Xiaoqin Lu, Xiao Liu, Wei Wang, Douglas C Dean, Henry J Kaplan, Ling Gao, Fangtian Dong, Yongqing Liu
Müller cells are the major supportive and protective glial cells in the retina with important functions in histogenesis and synaptogenesis during development, and in maintenance of mature neurons as they show to secrete various cytokines and manifest potentials of self-renewal and transdifferentiation into retinal neurons following injury in the vertebrate retinas. The swine retina has a visual streak structure similar to the human macular where cone photoreceptors are highly concentrated, thereby can serve as a better model for studying retinal diseases and for formulating cell-based therapeutics than the rodent retinas...
February 2, 2017: Stem Cells
https://www.readbyqxmd.com/read/28115389/hypo-methylation-mediates-chromosomal-instability-in-pancreatic-net
#10
I Marinoni, A Wiederkeher, T Wiedmer, S Pantasis, A Di Domenico, R Frank, E Vassella, A Schmitt, A Perren
DAXX and or ATRX loss occur in 40% of pancreatic neuroendocrine tumors (PanNETs). PanNETs negative for DAXX or ATRX show an increased risk of relapse. The tumor-associated pathways activated upon DAXX or ATRX loss and how this event may induce chromosomal instability (CIN) and alternative lengthening telomeres (ALT) are still unknown. Both DAXX and ATRX are involved in DNA methylation regulation. DNA methylation of heterochromatin and of non-coding sequences is extremely important for the maintenance of genomic stability...
March 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28064387/the-role-of-histone-modifications-and-telomere-alterations-in-the-pathogenesis-of-diffuse-gliomas-in-adults-and-children
#11
REVIEW
Julieann Lee, David A Solomon, Tarik Tihan
Genetic profiling is an increasingly useful tool for sub-classification of gliomas in adults and children. Specific gene mutations, structural rearrangements, DNA methylation patterns, and gene expression profiles are now recognized to define molecular subgroups of gliomas that arise in distinct anatomic locations and patient age groups, and also provide a better prediction of clinical outcomes for glioma patients compared to histologic assessment alone. Understanding the role of these distinctive genetic alterations in gliomagenesis is also important for the development of potential targeted therapeutic interventions...
March 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28040793/tert-promoter-mutations-but-not-the-alternative-lengthening-of-telomeres-phenotype-are-present-in-a-subset-of-ependymomas-and-are-associated-with-adult-onset-and-progression-to-ependymosarcoma
#12
Fabienne Brügger, Matthias S Dettmer, Maja Neuenschwander, Aurel Perren, Ilaria Marinoni, Ekkehard Hewer
Genetic signatures related to telomere maintenance have emerged as powerful classifiers among CNS tumors. These include the alternative lengthening of telomeres (ALT) phenotype associated with mutations in the ATRX and DAXX genes and recurrent point mutations in the TERT gene promoter. We investigated a patient cohort covering the entire spectrum of childhood and adult ependymomas (n = 128), including subependymomas and myxopapillary ependymomas, for the presence of TERT promoter mutations, for loss of ATRX or DAXX expression by immunohistochemistry (as surrogates as underlying gene mutations), and for the ALT phenotype by fluorescence in situ hybridization (FISH)...
January 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27943596/the-telomere-lengthening-conundrum-it-could-be-biology
#13
Melissa Bateson, Daniel Nettle
Longitudinal studies of human leucocyte telomere length often report a percentage of individuals whose telomeres appear to lengthen. However, based on theoretical considerations and empirical data, Steenstrup et al. (Nucleic Acids Research, 2013, vol 41(13): e131) concluded that this lengthening is unlikely to be a real biological phenomenon and is more likely to be an artefact of measurement error. We dispute the logic underlying this claim. We argue that Steenstrup et al.'s analysis is incomplete because it failed to compare predictions derived from assuming a scenario with no true telomere lengthening with alternative scenarios in which true lengthening occurs...
April 2017: Aging Cell
https://www.readbyqxmd.com/read/27892716/life-and-cancer-without-telomerase-alt-and-other-strategies-for-making-sure-ends-don-t-meet
#14
Manasi S Apte, Julia Promisel Cooper
While most cancer cells rely on telomerase expression/re-activation for linear chromosome maintenance and sustained proliferation, a significant population of cancers (10-15%) employs telomerase-independent strategies, collectively dubbed Alternative Lengthening of Telomeres (ALT). Most ALT cells relax the usual role of telomeres as inhibitors of local homologous recombination while maintaining the ability of telomeres to prohibit local non-homologous end joining reactions. Here we review current concepts surrounding how ALT telomeres achieve this new balance via alterations in chromatin landscape, DNA damage repair processes and handling of telomeric transcription...
November 28, 2016: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27889084/linking-telomere-regulation-to-stem-cell-pluripotency
#15
REVIEW
Lin Liu
Embryonic stem cells (ESCs), somatic cell nuclear transfer ESCs, and induced pluripotent stem cells (iPSCs) represent the most studied group of PSCs. Unlimited self-renewal without incurring chromosomal instability and pluripotency are essential for the potential use of PSCs in regenerative therapy. Telomere length maintenance is critical for the unlimited self-renewal, pluripotency, and chromosomal stability of PSCs. While telomerase has a primary role in telomere maintenance, alternative lengthening of telomere pathways involving recombination and epigenetic modifications are also required for telomere length regulation, notably in mouse PSCs...
January 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27833022/hdac9-regulates-the-alternative-lengthening-of-telomere-alt-pathway-via-the-formation-of-alt-associated-pml-bodies
#16
Mohd Raeed Jamiruddin, Taku Kaitsuka, Farzana Hakim, Atsushi Fujimura, Fan-Yan Wei, Hisato Saitoh, Kazuhito Tomizawa
Cancer cells overcome cellular senescence by activating the telomere maintenance mechanism, which can be either through telomerase or the alternative lengthening of telomeres (ALT). Being exclusive to cancer cells, targeting ALT is a more promising route for the development of drugs against cancer. The histone deacetylase (HDAC) family plays significant roles in various cellular processes. In addition to the regulation of gene expression, HDACs are also known to directly interact with many proteins. We focused on this family, and found that HDAC9 was up-regulated in ALT-positive cells...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27829156/proteomic-profiling-reveals-a-specific-role-for-translesion-dna-polymerase-%C3%AE-in-the-alternative-lengthening-of-telomeres
#17
Laura Garcia-Exposito, Elodie Bournique, Valérie Bergoglio, Arindam Bose, Jonathan Barroso-Gonzalez, Sufang Zhang, Justin L Roncaioli, Marietta Lee, Callen T Wallace, Simon C Watkins, Patricia L Opresko, Jean-Sébastien Hoffmann, Roderick J O'Sullivan
Cancer cells rely on the activation of telomerase or the alternative lengthening of telomeres (ALT) pathways for telomere maintenance and survival. ALT involves homologous recombination (HR)-dependent exchange and/or HR-associated synthesis of telomeric DNA. Utilizing proximity-dependent biotinylation (BioID), we sought to determine the proteome of telomeres in cancer cells that employ these distinct telomere elongation mechanisms. Our analysis reveals that multiple DNA repair networks converge at ALT telomeres...
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27821557/telomeres-reproductive-aging-and-genomic-instability-during-early-development
#18
David L Keefe
Implantation rate decreases and miscarriage rate increases with advancing maternal age. The oocyte must be the locus of reproductive aging because donation of oocytes from younger to older women abrogates the effects of aging on fecundity. Nuclear transfer experiments in a mouse model of reproductive aging show that the reproductive aging phenotype segregates with the nucleus rather than the cytoplasm. A number of factors within the nucleus have been hypothesized to mediate reproductive aging, including disruption of cohesions, reduced chiasma, aneuploidy, disrupted meiotic spindles, and DNA damage caused by chronic exposure to reactive oxygen species...
December 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27806302/telomere-internal-double-strand-breaks-are-repaired-by-homologous-recombination-and-parp1-lig3-dependent-end-joining
#19
Ylli Doksani, Titia de Lange
Shelterin protects chromosome ends from the DNA damage response. Although the mechanism of telomere protection has been studied extensively, the fate of double-strand breaks (DSBs) inside telomeres is not known. Here, we report that telomere-internal FokI-induced DSBs activate ATM kinase-dependent signaling in S-phase but are well tolerated and repaired efficiently. Homologous recombination contributes to repair, leading to increased telomere length heterogeneity typical of the alternative lengthening of telomeres (ALT) pathway...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27793809/alternative-lengthening-of-telomeres-requires-a-specialized-replisome
#20
(no author information available yet)
A specialized replisome mediates break-induced telomere synthesis to promote telomere maintenance.
December 2016: Cancer Discovery
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