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https://www.readbyqxmd.com/read/27871246/functional-characterization-of-thiolase-encoding-genes-from-xanthophyllomyces-dendrorhous-and-their-effects-on-carotenoid-synthesis
#1
Nicole Werner, Melissa Gómez, Marcelo Baeza, Víctor Cifuentes, Jennifer Alcaíno
BACKGROUND: The basidiomycetous yeast Xanthophyllomyces dendrorhous has been described as a potential biofactory for terpenoid-derived compounds due to its ability to synthesize astaxanthin. Functional knowledge of the genes involved in terpenoid synthesis would create opportunities to enhance carotenoid production. A thiolase enzyme catalyzes the first step in terpenoid synthesis. RESULTS: Two potential thiolase-encoding genes were found in the yeast genome; bioinformatically, one was identified as an acetyl-CoA C-acetyltransferase (ERG10), and the other was identified as a 3-ketoacyl Co-A thiolase (POT1)...
November 21, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27869169/critical-role-of-the-pot1-ob-domain-in-maintaining-genomic-stability
#2
T K Pandita
Oligonucleotide/oligosaccharide-binding (OB) domain-containing proteins have been identified as critical for telomere maintenance, DNA repair, transcription and other DNA metabolism processes. Protection of telomere 1 (POT1), a telomere binding protein, has an OB domain like single-strand binding protein (SSB1). In this issue of Oncogene, Gu et al. present evidence that POT1, like SSB1, is required to maintain genomic stability. This work, in conjunction with results from previous investigators, highlights the importance of POT1 in telomere metabolism...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27869160/pot1-ob-fold-mutations-unleash-telomere-instability-to-initiate-tumorigenesis
#3
P Gu, Y Wang, K K Bisht, L Wu, L Kukova, E M Smith, Y Xiao, S M Bailey, M Lei, J Nandakumar, S Chang
Chromosomal aberrations are a hallmark of human cancers, with complex cytogenetic rearrangements leading to genetic changes permissive for cancer initiation and progression. Protection of Telomere 1 (POT1) is an essential component of the shelterin complex and functions to maintain chromosome stability by repressing the activation of aberrant DNA damage and repair responses at telomeres. Sporadic and familial mutations in the oligosaccharide-oligonucleotide (OB) folds of POT1 have been identified in many human cancers, but the mechanism underlying how hPOT1 mutations initiate tumorigenesis has remained unclear...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27835648/mtv-an-ssdna-protecting-complex-essential-for-transposon-based-telomere-maintenance-in-drosophila
#4
Yi Zhang, Liang Zhang, Xiaona Tang, Shilpa R Bhardwaj, Jingyun Ji, Yikang S Rong
Multiple complexes protect telomeres. In telomerase-maintained organisms, Shelterin related complexes occupy the duplex region while the CST and Tpp1-Pot1 complexes bind the single stranded overhang of telomeres. Drosophila uses a transposon-based mechanism for end protection. We showed that the HOAP-HipHop complex occupies the duplex region. Whether an ssDNA-binding complex exists is not known. Here we discover a novel protein, Tea, that is specifically enriched at telomeres to prevent telomere fusion. We also identify a complex consisting of Tea and two known capping proteins, Ver and Moi...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27785368/ercc1-and-telomere-status-in-breast-tumours-treated-with-neoadjuvant-chemotherapy-and-their-association-with-patient-prognosis
#5
Mathilde Gay-Bellile, Pierre Romero, Anne Cayre, Lauren Véronèse, Maud Privat, Shalini Singh, Patricia Combes, Fabrice Kwiatkowski, Catherine Abrial, Yves-Jean Bignon, Philippe Vago, Frédérique Penault-Llorca, Andreï Tchirkov
Dysfunctional telomeres and DNA damage repair (DDR) play important roles in cancer progression. Studies have reported correlations between these factors and tumour aggressiveness and clinical outcome in breast cancer. We studied the characteristics of telomeres and expression of ERCC1, a protein involved in a number of DNA repair pathways and in telomere homeostasis, to assess their prognostic value, alone or in combination, in 90 residual breast tumours after treatment with neoadjuvant chemotherapy (NCT). ERCC1 status was investigated at different molecular levels (protein and gene expression and gene copy-number variations) by immunohistochemistry, qRT-PCR and quantitative multiplex fluorescent-PCR (QMF-PCR)...
October 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27782152/hulc-cooperates-with-malat1-to-aggravate-liver-cancer-stem-cells-growth-through-telomere-repeat-binding-factor-2
#6
Mengying Wu, Zhuojia Lin, Xiaonan Li, Xiaoru Xin, Jiahui An, Qidi Zheng, Yuxin Yang, Dongdong Lu
The dysregulation of lncRNAs has increasingly been linked to many human diseases, especially in cancers. Our results demonstrate HULC, MALAT1 and TRF2 are highly expressed in human hepatocellular carcinoma tissues, and HULC plus MALAT1 overexpression drastically promotes the growth of liver cancer stem cells. Mechanistically, both HULC and MALAT1 overexpression enhanced RNA polII, P300, CREPT to load on the promoter region of telomere repeat-binding factor 2(TRF2), triggering the overexpression, phosphorylation and SUMOylation of TRF2...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27776349/genetic-profiling-of-a-rare-condition-co-occurrence-of-albinism-and-multiple-primary-melanoma-in-a-caucasian-family
#7
Simona De Summa, Michele Guida, Stefania Tommasi, Sabino Strippoli, Cristina Pellegrini, Maria Concetta Fargnoli, Brunella Pilato, Iole Natalicchio, Gabriella Guida, Rosamaria Pinto
Multiple primary melanoma (MPM) is a rare condition, whose genetic basis has not yet been clarified. Only 8-12% of MPM are due to germline mutations of CDKN2A. However, other genes (POT1, BRCA1/2, MC1R, MGMT) have been demonstrated to be involved in predisposition to this pathology.To our knowledge, this is the first family study based on two siblings with the rare coexistence of MPM and oculocutaneous albinism (OCA), an autosomal recessive disease characterized by the absence or decrease in pigmentation in the skin, hair, and eyes...
October 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27655633/dynamic-peptides-of-human-tpp1-fulfill-diverse-functions-in-telomere-maintenance
#8
Malligarjunan Rajavel, Tivadar Orban, Mengyuan Xu, Wilnelly Hernandez-Sanchez, Maria de la Fuente, Krzysztof Palczewski, Derek J Taylor
Telomeres are specialized nucleoprotein complexes that comprise the ends of linear chromosomes. Human telomeres end in a short, single-stranded DNA (ssDNA) overhang that is recognized and bound by two telomere proteins, POT1 and TPP1. Whereas POT1 binds directly to telomere ssDNA, its interaction with TPP1 is essential for localization of POT1 to the telomere. TPP1 also provides enhanced binding and sequence discrimination that regulates POT1-TPP1 interactions exclusively with telomere ssDNA. Finally, TPP1 recruits telomerase, the enzyme responsible for synthesis of telomere DNA, to the telomere...
September 20, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27655175/a-new-eif4e1-allele-characterized-by-rnaseq-data-mining-is-associated-with-resistance-to-potato-virus-y-in-tomato-albeit-with-a-low-durability
#9
Caroline Lebaron, Aurélie Rosado, Christopher Sauvage, Camille Gauffier, Sylvie German-Retana, Benoît Moury, Jean-Luc Gallois
Allele mining on susceptibility factors offers opportunities to find new sources of resistance among crop wild relatives for breeding purposes. As a proof of concept, we used available RNAseq data to investigate polymorphisms among the four tomato genes encoding translation initiation factors [eIF4E1 and eIF4E2, eIFiso4E and the related gene new cap-binding protein(nCBP)] to look for new potential resistance alleles to potyviruses. By analysing polymorphism among RNAseq data obtained for 20 tomato accessions, 10 belonging to the cultivated type Solanum lycopersicum and 10 belonging to the closest related wild species Solanum pimpinellifolium, we isolated one new eIF4E1 allele, in the S...
November 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27654173/smedob1-is-required-for-planarian-homeostasis-and-regeneration
#10
Shanshan Yin, Yan Huang, Yingnan Zhangfang, Xiaoqin Zhong, Pengqing Li, Junjiu Huang, Dan Liu, Zhou Songyang
The planarian flatworm is an emerging model that is useful for studying homeostasis and regeneration due to its unique adult stem cells (ASCs). Previously, planaria were found to share mammalian TTAGGG chromosome ends and telomerases; however, their telomere protection proteins have not yet been identified. In Schmidtea mediterranea, we identified a homologue of the human protection of telomeres 1 (POT1) with an OB-fold (SmedOB1). SmedOB1 is evolutionarily conserved among species and is ubiquitously expressed throughout the whole body...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27651456/evolution-of-arabidopsis-protection-of-telomeres-1-alters-nucleic-acid-recognition-and-telomerase-regulation
#11
Amit Arora, Mark A Beilstein, Dorothy E Shippen
Protection of telomeres (POT1) binds chromosome ends, recognizing single-strand telomeric DNA via two oligonucleotide/oligosaccharide binding folds (OB-folds). The Arabidopsis thaliana POT1a and POT1b paralogs are atypical: they do not exhibit telomeric DNA binding, and they have opposing roles in regulating telomerase activity. AtPOT1a stimulates repeat addition processivity of the canonical telomerase enzyme, while AtPOT1b interacts with a regulatory lncRNA that represses telomerase activity. Here, we show that OB1 of POT1a, but not POT1b, has an intrinsic affinity for telomeric DNA...
November 16, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27575340/tying-up-the-ends-plasticity-in-the-recognition-of-single-stranded-dna-at-telomeres
#12
Neil R Lloyd, Thayne H Dickey, Robert A Hom, Deborah S Wuttke
Telomeres terminate nearly exclusively in single-stranded DNA (ssDNA) overhangs comprised of the G-rich 3' end. This overhang varies widely in length from species to species, ranging from just a few bases to several hundred nucleotides. These overhangs are not merely a remnant of DNA replication but rather are the result of complex further processing. Proper management of the telomeric overhang is required both to deter the action of the DNA damage machinery and to present the ends properly to the replicative enzyme telomerase...
September 27, 2016: Biochemistry
https://www.readbyqxmd.com/read/27528712/germline-mutations-in-shelterin-complex-genes-are-associated-with-familial-chronic-lymphocytic-leukemia
#13
Helen E Speedy, Ben Kinnersley, Daniel Chubb, Peter Broderick, Philip J Law, Kevin Litchfield, Sandrine Jayne, Martin J S Dyer, Claire Dearden, George A Follows, Daniel Catovsky, Richard S Houlston
Chronic lymphocytic leukemia (CLL) can be familial, however thus far no rare germline disruptive alleles for CLL have been identified. We performed whole-exome sequencing of 66 CLL families, identifying four families where loss-of-function mutations in POT1 co-segregated with CLL. The p.Tyr36Cys mutation is predicted to disrupt the interaction between POT1 and the telomeric overhang. The c.1164-1G>A splice-site, p.Gln358SerfsTer13 frameshift and p.Gln376Arg missense mutations are likely to impact the interaction between POT1 and ACD, part of the telomere-capping shelterin complex...
August 15, 2016: Blood
https://www.readbyqxmd.com/read/27500188/telomere-dysfunction-induced-foci-tif-analysis
#14
Ilgen Mender, Jerry W Shay
Telomerase maintains telomeric DNA in eukaryotes during early developments, ~90% of cancer cells and some proliferative stem like cells. Telomeric repeats at the end of chromosomes are associated with the shelterin complex. This complex consists of TRF1, TRF2, Rap1, TIN2, TPP1, POT1 which protect DNA from being recognized as DNA double-stranded breaks. Critically short telomeres or impaired shelterin proteins can cause telomere dysfunction, which eventually induces DNA damage responses at the telomeres. DNA damage responses can be identified by antibodies to 53BP1, gammaH2AX, Rad17, ATM, and Mre11...
November 20, 2015: Bio-protocol
https://www.readbyqxmd.com/read/27486974/telomere-status-in-chronic-lymphocytic-leukemia-with-tp53-disruption
#15
Romain Guièze, Mélanie Pages, Lauren Véronèse, Patricia Combes, Richard Lemal, Mathilde Gay-Bellile, Martine Chauvet, Mary Callanan, Fabrice Kwiatkowski, Bruno Pereira, Philippe Vago, Jacques-Olivier Bay, Olivier Tournilhac, Andreï Tchirkov
In chronic lymphocytic leukemia (CLL), telomere dysfunction is associated with poor outcomes. TP53 is involved in cellular responses to dysfunctional telomeres, and its inactivation is the strongest adverse prognostic factor for CLL. Given the biological relationship between TP53 and telomeres, and their prognostic value, it is important to improve our understanding of the impact of TP53 alterations on telomeres. We performed a comprehensive study of the deletions and mutations of the TP53 gene and telomere parameters, including hTERT and the shelterin complex, in 115 CLL patients...
July 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27455024/-advance-in-research-on-the-function-of-telomeric-shelterin-component-tpp1-and-its-relationship-with-characteristics-of-tumors
#16
REVIEW
Lihua Yao, Xiaolan Guo
As an important telomere binding protein, TPP1 protects the ends of telomeres and maintains the stability and integrity of its structure and function by interacting with other five essential core proteins (POT1, TRF1, TRF2, TIN2, and RAP1) to form a complex called Shelterin. Recently, researchers have discovered that TPP1 participates in protection of telomeres and regulation of telomerase activity. The relationship between TPP1 and tumorigenesis, tumor progression and treatment has also been investigated. This paper reviews the latest findings of TPP1 regarding to its structure, function and interaction with other proteins involved in tumorigenesis...
August 2016: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/27450562/molecular-basis-and-quantitative-assessment-of-trf1-and-trf2-protein-interactions-with-tin2-and-apollo-peptides
#17
Umesh Kalathiya, Monikaben Padariya, Maciej Baginski
Shelterin is a six-protein complex (TRF1, TRF2, POT1, RAP1, TIN2, and TPP1) that also functions in smaller subsets in regulation and protection of human telomeres. Two closely related proteins, TRF1 and TRF2, make high-affinity contact directly with double-stranded telomeric DNA and serve as a molecular platform. Protein TIN2 binds to TRF1 and TRF2 dimer-forming domains, whereas Apollo makes interaction only with TRF2. To elucidate the molecular basis of these interactions, we employed molecular dynamics (MD) simulations of TRF1TRFH-TIN2TBM and TRF2TRFH-TIN2TBM/ApolloTBM complexes and of the isolated proteins...
July 22, 2016: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/27419638/stressed-telomeres-without-pot1-enhance-tumorigenesis
#18
EDITORIAL
Agnel Sfeir, Eros Lazzerini Denchi
No abstract text is available yet for this article.
July 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27396482/nek6-mediated-phosphorylation-of-human-tpp1-regulates-telomere-length-through-telomerase-recruitment
#19
Yugo Hirai, Miki Tamura, Junji Otani, Fuyuki Ishikawa
Shelterin component TPP1 plays critical roles in chromosome end protection and telomere length regulation. Specifically, TPP1 contains an OB-fold domain that provides an interface to recruit telomerase. However, it remains largely unknown how telomerase recruitment is regulated by cell cycle regulators. We show that TPP1 interacts with the cell cycle regulator kinase NEK6 in human cells. We found that NEK6-mediated phosphorylation of TPP1 Ser255 in G2/M phase regulates the association between telomerase activity and TPP1...
August 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/27329137/rare-disruptive-mutations-and-their-contribution-to-the-heritable-risk-of-colorectal-cancer
#20
Daniel Chubb, Peter Broderick, Sara E Dobbins, Matthew Frampton, Ben Kinnersley, Steven Penegar, Amy Price, Yussanne P Ma, Amy L Sherborne, Claire Palles, Maria N Timofeeva, D Timothy Bishop, Malcolm G Dunlop, Ian Tomlinson, Richard S Houlston
Colorectal cancer (CRC) displays a complex pattern of inheritance. It is postulated that much of the missing heritability of CRC is enshrined in high-impact rare alleles, which are mechanistically and clinically important. In this study, we assay the impact of rare germline mutations on CRC, analysing high-coverage exome sequencing data on 1,006 early-onset familial CRC cases and 1,609 healthy controls, with additional sequencing and array data on up to 5,552 cases and 6,792 controls. We identify highly penetrant rare mutations in 16% of familial CRC...
June 22, 2016: Nature Communications
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