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Balal Brazvan, Abbas Ebrahimi-Kalan, Kobra Velaei, Ahmad Mehdipour, Zeynab Aliyari Serej, Ayyub Ebrahimi, Mohammad Ghorbani, Omid Cheraghi, Hojjatollah Nozad Charoudeh
The end of linear chromosomes is formed of a special nucleoprotein heterochromatin structure with repetitive TTAGGG sequences called telomere. Telomere length is regulated by a special enzyme called telomerase, a specific DNA polymerase that adds new telomeric sequences to the chromosome ends. Telomerase consists of two parts; the central protein part and the accessory part which is a RNA component transported by the central part. Regulation of telomere length by this enzyme is a multi-stage process. Telomere length elongation is strongly influenced by the level of telomerase and has a strong correlation with the activity of telomerase enzyme...
March 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jimena López-Arrabé, Pat Monaghan, Alejandro Cantarero, Winnie Boner, Lorenzo Pérez-Rodríguez, Juan Moreno
Oxidative stress can contribute to an acceleration of telomere erosion, leading to cellular senescence and aging. Increased investment in reproduction is known to accelerate senescence, generally resulting in reduced future reproductive potential and survival. To better understand the role played by oxidative status and telomere dynamics in the conflict between maintenance and reproduction, it is important to determine how these factors are related in parents and their offspring. We investigated the relationship between oxidative status and telomere measurements in pied flycatchers (Ficedula hypoleuca)...
May 2018: Physiological and Biochemical Zoology: PBZ
Richard Garrett Morgan, Anthony J Donato, Ashley E Walker
While most telomere biology research continues to focus on telomere shortening, there is increasing evidence that telomere deprotection, or "uncapping", is more biologically and possibly clinically important. Telomeres form t-loops to prevent the chromosome ends from appearing as a double-stranded DNA break and initiating a DNA damage response. Breakdown of the t-loop structure, referred to as uncapping, can lead to cellular senescence and increased oxidative stress and inflammation in tissues. In this review, we will describe how telomere uncapping potentially leads to age-related vascular dysfunction, and increased cellular senescence, oxidative stress, and inflammation...
March 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Hua Zhou, Abdul Mondal, Aleksandra Dakic, Lama Alhawas, Xuefeng Liu, Zhixu He
The roles of protection of telomeres 1 (POT1) in human ovarian cancer have not been fully elucidated. Here, we investigated the impact of POT1 knockdown (POT1-KD) on in vitro cell proliferation, tumorigenesis, and histone deacetylase inhibitor (HDACi) response in human ovarian cancer-derived SK-OV3 cells. The POT1 gene was knocked down by infection with POT1 lenti-shRNA. POT1, c-Myc, and hTERT mRNA levels and relative telomere length were determined by qRT-PCR; POT1 protein levels were determined by western blot...
2018: BioMed Research International
Marco A Moro-García, Juan C Mayo, Rosa M Sainz, Rebeca Alonso-Arias
T lymphocytes, from their first encounter with their specific antigen as naïve cell until the last stages of their differentiation, in a replicative state of senescence, go through a series of phases. In several of these stages, T lymphocytes are subjected to exponential growth in successive encounters with the same antigen. This entire process occurs throughout the life of a human individual and, earlier, in patients with chronic infections/pathologies through inflammatory mediators, first acutely and later in a chronic form...
2018: Frontiers in Immunology
Joydeep Mukherjee, Tor-Christian Aase Johannessen, Shigeo Ohba, Tracy T Chow, Lindsey E Jones, Ajay Pandita, Russell O Pieper
A subset of tumors use a recombination-based alternative lengthening of telomere (ALT) pathway to resolve telomeric dysfunction in the absence of TERT. Loss-of-function mutations in the chromatin remodeling factor ATRX are associated with ALT but are insufficient to drive the process. Because many ALT tumors express the mutant isocitrate dehydrogenase IDH1 R132H, including all lower-grade astrocytomas (LGA) and secondary glioblastoma, we examined an hypothesized role for IDH1 R132H in driving the ALT phenotype during gliomagenesis...
March 15, 2018: Cancer Research
Amanda A Soares, Jonathan P Castro, Pedro Balieiro, Sidnei Dornelles, Tiago M Degrandi, Ives J Sbalqueiro, Roberto Ferreira Artoni, Iris Hass
B chromosomes are supernumerary chromosomes found in the karyotypes of approximately 15% of all eukaryotic species. They present parasitic behavior and do not follow the standard Mendelian pattern of inheritance, resulting in an imbalance in gametogenesis. The evolutionary dynamics of B chromosomes is still unknown for many species, but studies indicate that the accumulation of repetitive sequences plays an important role in the differentiation of these elements. We analyzed morphology, frequency, and possible homologies amongst different B chromosomes found in an isolated Akodon montensis population in southern Brazil...
March 16, 2018: Cytogenetic and Genome Research
Jinyu Wang, Haitao Zhang, Mohammed Al Shibar, Belinda Willard, Alo Ray, Kurt W Runge
Telomeres, the ends of eukaryotic chromosomes, consist of repetitive DNA sequences and their bound proteins that protect the end from the DNA damage response. Short telomeres with fewer repeats are preferentially elongated by telomerase. Tel1, the yeast homolog of human ATM kinase, is preferentially recruited to short telomeres and Tel1 kinase activity is required for telomere elongation. Rif1, a telomere-binding protein, negatively regulates telomere length by forming a complex with two other telomere binding proteins, Rap1 and Rif2, to block telomerase recruitment...
March 7, 2018: DNA Repair
Pingping Jia, Weihang Chai
Genome instability gives rise to cancer. MLH1, commonly known for its important role in mismatch repair (MMR), DNA damage signaling and double-strand break (DSB) repair, safeguards genome stability. Recently we have reported a novel role of MLH1 in preventing aberrant formation of interstitial telomeric sequences (ITSs) at intra-chromosomal regions. Deficiency in MLH1, in particular its N-terminus, leads to an increase of ITSs. Here, we identify that the ATPase activity in the MLH1 N-terminal domain is important for suppressing the formation of ITSs...
March 7, 2018: DNA Repair
Nedime Serakinci, Huseyin Cagsin, Merdiye Mavis
Telomeres are repetitive genetic materials that protect the chromosomes by capping the ends of chromosomes. Each time a cell divides, telomeres get shorter. Telomere length is mainly maintained by telomerase. This enzyme is present in the embryonic stem cells in high concentrations and declines with age. It is still unclear to what extend there is telomerase in adult stem cells, but considering these are the founder cells to the cells of the all tissues in a body, understanding the telomere dynamics and expression of telomerase in adult stem cells is very important...
March 15, 2018: Methods in Molecular Biology
José C Noguera, Neil B Metcalfe, Pat Monaghan
Offspring of older parents frequently show reduced longevity, but the mechanisms driving this so-called 'Lansing effect' are unknown. While inheritance of short telomeres from older parents could underlie this effect, studies to date in different species have found mixed results, reporting positive, negative or no association between parental age and offspring telomere length (TL). However, most of the existing evidence is from non-experimental studies in which it is difficult to exclude alternative explanations such as differential survival of parents with different telomere lengths...
March 14, 2018: Proceedings. Biological Sciences
Sara Silva Pereira, Andrew P Jackson
BACKGROUND: Trypanosomatid parasites such as Trypanosoma spp. and Leishmania spp. are a major source of infectious disease in humans and domestic animals worldwide. Fundamental to the host-parasite interactions of these potent pathogens are their cell surfaces, which are highly decorated with glycosylated proteins and other macromolecules. Trypanosomatid genomes contain large multi-copy gene families encoding UDP-dependent glycosyltransferases (UGTs), the primary role of which is cell-surface decoration...
March 14, 2018: BMC Evolutionary Biology
Reinier Snetselaar, Matthijs F M van Oosterhout, Jan C Grutters, Coline H M van Moorsel
The enzyme telomerase reverse transcriptase (TERT) is essential for telomere maintenance. In replicating cells, maintenance of telomere length is important for the preservation of vital genetic information and prevention of genomic instability. A common genetic variant in TERT , rs2736100 C/A, is associated with both telomere length and multiple diseases. Carriage of the C allele is associated with longer telomere length, while carriage of the A allele is associated with shorter telomere length. Furthermore, some diseases have a positive association with the C and some with the A allele...
2018: Frontiers in Medicine
Carla Danussi, Promita Bose, Prasanna T Parthasarathy, Pedro C Silberman, John S Van Arnam, Mark Vitucci, Oliver Y Tang, Adriana Heguy, Yuxiang Wang, Timothy A Chan, Gregory J Riggins, Erik P Sulman, Frederick Lang, Chad J Creighton, Benjamin Deneen, C Ryan Miller, David J Picketts, Kasthuri Kannan, Jason T Huse
Mutational inactivation of the SWI/SNF chromatin regulator ATRX occurs frequently in gliomas, the most common primary brain tumors. Whether and how ATRX deficiency promotes oncogenesis by epigenomic dysregulation remains unclear, despite its recent implication in both genomic instability and telomere dysfunction. Here we report that Atrx loss recapitulates characteristic disease phenotypes and molecular features in putative glioma cells of origin, inducing cellular motility although also shifting differentiation state and potential toward an astrocytic rather than neuronal histiogenic profile...
March 13, 2018: Nature Communications
Yakai Song, Linjuan Li, Yantao Chen, Jingqiu Liu, Senhao Xiao, Fulin Lian, Naixia Zhang, Hong Ding, Yuanyuan Zhang, Kaixian Chen, Hualiang Jiang, Chenhua Zhang, Yu-Chih Liu, Shijie Chen, Cheng Luo
DOT1L (the disruptor of telomeric silencing 1-like), through its methyltransferase activity of H3K79, plays essential roles in transcriptional regulation, cell cycle regulation, and DNA damage response. In addition, DOT1L is believed to be involved in the development of MLL-rearranged leukemia driven by the MLL (mixed-lineage leukemia) fusion proteins, which thus to be a crucial target for leukemia therapy. Hence, discovering of novel DOT1L inhibitors has been in a great demand. In this study, we initiated the discovering process from setting up the AlphaLISA based High Throughput Screening (HTS) assay of DOT1L...
February 24, 2018: Bioorganic & Medicinal Chemistry
Nabeel Quryshi, Laura E Norwood Toro, Karima Ait-Aissa, Amanda Kong, Andreas M Beyer
Although chemotherapeutics can be highly effective at targeting malignancies, their ability to trigger cardiovascular morbidity is clinically significant. Chemotherapy can adversely affect cardiovascular physiology, resulting in the development of cardiomyopathy, heart failure and microvascular defects. Specifically, anthracyclines are known to cause an excessive buildup of free radical species and mitochondrial DNA damage (mt DNA) that can lead to oxidative stress-induced cardiovascular apoptosis. Therefore, oncologists and cardiologists maintain a network of communication when dealing with patients during treatment in order to treat and prevent chemotherapy-induced cardiovascular damage; however, there is a need to discover more accurate biomarkers and therapeutics to combat and predict the onset of cardiovascular side effects...
March 10, 2018: International Journal of Molecular Sciences
Ami R Zota, Ruth J Geller, Laura E Romano, Kimberly Coleman-Phox, Nancy E Adler, Emily Parry, Miaomiao Wang, June-Soo Park, Angelo F Elmi, Barbara A Laraia, Elissa S Epel
BACKGROUND: Endocrine-disrupting chemicals (EDCs) can target immune and metabolic pathways. However, few epidemiologic studies have examined the influence of EDCs on measures of inflammation and cellular aging during pregnancy and postpartum. OBJECTIVE: We investigated associations between prenatal exposures to polybrominated diphenyl ethers (PBDEs), hydroxylated PBDE metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and per- and polyfluorochemicals (PFASs) with repeated biomarker measurements of inflammation and cellular aging in women during pregnancy and the postpartum period...
March 10, 2018: Environment International
Takuya Furuta, Hiroaki Miyoshi, Satoru Komaki, Fumiko Arakawa, Motohiro Morioka, Koichi Ohshima, Mitsutoshi Nakada, Yasuo Sugita
Epithelioid glioblastoma (eGBM) is a rare variant of GBM which was adopted in the 2016 WHO classification. eGBM and pleomorphic xanthoastrocytoma (PXA) sometimes show overlapping features histologically and genetically, such as epithelioid pattern and a highly frequent V600E mutation in the gene for vRAF murine sarcoma viral oncogene homolog B1 (BRAF), respectively. Accurate diagnosis of these rare tumors is challenging according to the new criteria in the revised 2016 WHO classification. It is an urgent task to elucidate the biological properties of the tumors and to select appropriate treatment...
March 13, 2018: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Ke-Zheng Dai, James C Ryan, Christian Naper, John T Vaage
Early studies indicate that rats may have a repertoire of MHC class Ib-reactive Ly49 stimulatory receptors capable of mounting memory-like NK cell alloresponses. In this article, we provide molecular and functional evidence for this assumption. Pairs of Ly49 receptors with sequence similarities in the lectin-like domains, but with opposing signaling functions, showed specificity for ligands with class Ia-like structural features encoded from the first telomeric MHC class Ib gene cluster, RT1-CE , which is syntenic with the H2-D/H2-L/H2-Q cluster in mice...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Aernoud A van Batenburg, Karin M Kazemier, Ton Peeters, Matthijs F M van Oosterhout, Joanne J van der Vis, Jan C Grutters, Roel Goldschmeding, Coline H M van Moorsel
Telomeres are small repetitive DNA sequences at the ends of chromosomes which act as a buffer in age-dependent DNA shortening. Insufficient telomere repeats will be recognized as double-strand breaks. Presently, it is becoming more evident that telomere attrition, whether or not caused by mutations in telomere maintenance genes, plays an important role in many inflammatory and age-associated diseases. In this report, a method to (semi)quantitatively assess telomere length and DNA double-strand breaks in formalin-fixed paraffin-embedded (FFPE) tissue is described...
March 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
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