The telomere lengthening mechanism in telomerase-negative immortal human cells does not involve the telomerase RNA subunit.

Abstract:

:According to the telomere hypothesis of senescence, the progressive shortening of telomeres that occurs upon division of normal somatic cells eventually leads to cellular senescence. The immortalisation of human cells is associated with the acquisition of a telomere maintenance mechanism which is usually dependent upon expression of the enzyme telomerase. About one third of in vitro immortalised human cell lines, however, have no detectable telomerase but contain telomeres that are abnormally long. The nature of the alternative telomere maintenance mechanism (referred to as ALT, for Alternative Lengthening of Telomeres) that must exist in these telomerase-negative cells has not been elucidated. It has previously been shown that abnormal lengthening of yeast telomeres may occur due to mutations in the yeast telomerase RNA gene. That this is not the mechanism of the abnormally long telomeres in ALT cell lines was demonstrated by the finding that seven of seven ALT lines have wild-type human telomerase RNA (hTR) sequence, including a novel polymorphism that is present in 30% of normal individuals. We found that two ALT cell lines have no detectable expression of the hTR gene. This shows that the ALT mechanism in these cell lines is not dependent on hTR. Expression of exogenous hTR via infection of these cells with a recombinant hTR-adenovirus vector did not result in telomerase activity, indicating that their lack of telomerase activity is not due to absence of hTR expression. We conclude that the ALT mechanism is not dependent on the expression of hTR, and does not involve mutations in the hTR sequence.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Bryan TM,Marusic L,Bacchetti S,Namba M,Reddel RR

doi

10.1093/hmg/6.6.921

subject

Has Abstract

pub_date

1997-06-01 00:00:00

pages

921-6

issue

6

eissn

0964-6906

issn

1460-2083

pii

dda125

journal_volume

6

pub_type

杂志文章
  • Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres.

    abstract::Multicentric chromosomes are often found in tumor cells and certain cell lines. How they are generated is not fully understood, though their stability suggests that they are non-functional during chromosome segregation. Growing evidence has implicated microtubule motor proteins in attachment of chromosomes to the mito...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/7.4.671

    authors: Faulkner NE,Vig B,Echeverri CJ,Wordeman L,Vallee RB

    更新日期:1998-04-01 00:00:00

  • Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.

    abstract::Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 males and 94 females and...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddv124

    authors: Rönn T,Volkov P,Gillberg L,Kokosar M,Perfilyev A,Jacobsen AL,Jørgensen SW,Brøns C,Jansson PA,Eriksson KF,Pedersen O,Hansen T,Groop L,Stener-Victorin E,Vaag A,Nilsson E,Ling C

    更新日期:2015-07-01 00:00:00

  • A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro alpha 1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I).

    abstract::Type V collagen is a constituent of type I collagen-rich fibrils in many connective tissues and is a regulator of fibril diameter. In tissues, type V collagen is a heterotrimer with the molecular structure: alpha 1(V)2 alpha 2(V) or alpha 1(V) alpha 2(V) alpha 3(V). We report that genomic polymorphisms at the pro alph...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/5.11.1733

    authors: Wenstrup RJ,Langland GT,Willing MC,D'Souza VN,Cole WG

    更新日期:1996-11-01 00:00:00

  • A conserved splicing mechanism of the LMNA gene controls premature aging.

    abstract::Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder phenotypically characterized by many features of premature aging. Most cases of HGPS are due to a heterozygous silent mutation (c.1824C>T; p.Gly608Gly) that enhances the use of an internal 5' splice site (5'SS) in exon 11 of the LMNA pre-mRNA and l...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddr385

    authors: Lopez-Mejia IC,Vautrot V,De Toledo M,Behm-Ansmant I,Bourgeois CF,Navarro CL,Osorio FG,Freije JM,Stévenin J,De Sandre-Giovannoli A,Lopez-Otin C,Lévy N,Branlant C,Tazi J

    更新日期:2011-12-01 00:00:00

  • Ca2+-permeable TRPV1 pain receptor knockout rescues memory deficits and reduces amyloid-β and tau in a mouse model of Alzheimer's disease.

    abstract::The transient receptor potential vanilloid 1 (TRPV1) protein is a pain receptor that elicits a hot sensation when an organism eats the capsaicin of red chili peppers. This calcium (Ca2+)-permeable cation channel is mostly expressed in the peripheral nervous system sensory neurons but also in the central nervous system...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddz276

    authors: Kim J,Lee S,Kim J,Ham S,Park JHY,Han S,Jung YK,Shim I,Han JS,Lee KW,Kim J

    更新日期:2020-01-15 00:00:00

  • Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation.

    abstract::The widespread use of persistent organic polybrominated diphenyl ethers (PBDEs) as commercial flame retardants has raised concern about potential long-lived effects on human health. Epigenetic mechanisms, such as DNA methylation, are responsive to environmental influences and have long-lasting consequences. Autism spe...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/dds046

    authors: Woods R,Vallero RO,Golub MS,Suarez JK,Ta TA,Yasui DH,Chi LH,Kostyniak PJ,Pessah IN,Berman RF,LaSalle JM

    更新日期:2012-06-01 00:00:00

  • Charcot-Marie-Tooth disease CMT4A: GDAP1 increases cellular glutathione and the mitochondrial membrane potential.

    abstract::Mutations in GDAP1 lead to recessively or dominantly inherited peripheral neuropathies (Charcot-Marie-Tooth disease, CMT), indicating that GDAP1 is essential for the viability of cells in the peripheral nervous system. GDAP1 contains domains characteristic of glutathione-S-transferases (GSTs), is located in the outer ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddr450

    authors: Noack R,Frede S,Albrecht P,Henke N,Pfeiffer A,Knoll K,Dehmel T,Meyer Zu Hörste G,Stettner M,Kieseier BC,Summer H,Golz S,Kochanski A,Wiedau-Pazos M,Arnold S,Lewerenz J,Methner A

    更新日期:2012-01-01 00:00:00

  • Assignment of a gene locus involved in craniosynostosis to chromosome 5qter.

    abstract::Craniosynostosis, the abnormal development of the calvarial sutures, occurs as an autosomal dominant trait in many clinically distinct syndromes. We performed linkage analysis of a provisionally novel type of autosomal dominant craniosynostosis in a large three generational family. Linkage was established between the ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/2.2.119

    authors: Müller U,Warman ML,Mulliken JB,Weber JL

    更新日期:1993-02-01 00:00:00

  • Human cis-acting elements regulating escape from X-chromosome inactivation function in mouse.

    abstract::A long-standing question concerning X-chromosome inactivation (XCI) has been how some genes avoid the otherwise stable chromosome-wide heterochromatinization of the inactive X chromosome. As 20% or more of human X-linked genes escape from inactivation, such genes are an important contributor to sex differences in gene...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddy039

    authors: Peeters SB,Korecki AJ,Simpson EM,Brown CJ

    更新日期:2018-04-01 00:00:00

  • Mutations in congenital myasthenic syndromes reveal an epsilon subunit C-terminal cysteine, C470, crucial for maturation and surface expression of adult AChR.

    abstract::Many congenital myasthenic syndromes (CMS) are associated with mutations in the genes encoding the acetylcholine receptor (AChR), an oligomeric protein with the structure alpha(2)betadelta epsilon. AChR deficiency is frequently due to homozygous or heteroallelic mutations in the AChR epsilon subunit, most of which cau...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/11.24.3087

    authors: Ealing J,Webster R,Brownlow S,Abdelgany A,Oosterhuis H,Muntoni F,Vaux DJ,Vincent A,Beeson D

    更新日期:2002-11-15 00:00:00

  • BRCA2 minor transcript lacking exons 4-7 supports viability in mice and may account for survival of humans with a pathogenic biallelic mutation.

    abstract::The breast cancer gene, BRCA2, is essential for viability, yet patients with Fanconi anemia-D1 subtype are born alive with biallelic mutations in this gene. The hypomorphic nature of the mutations is believed to support viability, but this is not always apparent. One such mutation is IVS7+2T>G, which causes premature ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddw066

    authors: Thirthagiri E,Klarmann KD,Shukla AK,Southon E,Biswas K,Martin BK,North SL,Magidson V,Burkett S,Haines DC,Noer K,Matthai R,Tessarollo L,Loncarek J,Keller JR,Sharan SK

    更新日期:2016-05-15 00:00:00

  • Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics.

    abstract::Induced pluripotent stem cell (iPSC)-derived cortical neurons potentially present a powerful new model to understand corticogenesis and neurological disease. Previous work has established that differentiation protocols can produce cortical neurons, but little has been done to characterize these at cellular resolution....

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddv637

    authors: Handel AE,Chintawar S,Lalic T,Whiteley E,Vowles J,Giustacchini A,Argoud K,Sopp P,Nakanishi M,Bowden R,Cowley S,Newey S,Akerman C,Ponting CP,Cader MZ

    更新日期:2016-03-01 00:00:00

  • Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25.

    abstract::Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddu511

    authors: Litchfield K,Sultana R,Renwick A,Dudakia D,Seal S,Ramsay E,Powell S,Elliott A,Warren-Perry M,Eeles R,Peto J,Kote-Jarai Z,Muir K,Nsengimana J,UKTCC.,Stratton MR,Easton DF,Bishop DT,Huddart RA,Rahman N,Turnbull C,

    更新日期:2015-02-15 00:00:00

  • NSDHL, an enzyme involved in cholesterol biosynthesis, traffics through the Golgi and accumulates on ER membranes and on the surface of lipid droplets.

    abstract::NSDHL, for NAD(P)H steroid dehydrogenase-like, encodes a sterol dehydrogenase or decarboxylase involved in the sequential removal of two C-4 methyl groups in post-squalene cholesterol biosynthesis. Mutations in this gene are associated with human CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and li...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddg321

    authors: Caldas H,Herman GE

    更新日期:2003-11-15 00:00:00

  • Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability.

    abstract::The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly r...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddw383

    authors: Breuss MW,Nguyen T,Srivatsan A,Leca I,Tian G,Fritz T,Hansen AH,Musaev D,McEvoy-Venneri J,James KN,Rosti RO,Scott E,Tan U,Kolodner RD,Cowan NJ,Keays DA,Gleeson JG

    更新日期:2017-01-15 00:00:00

  • Naturally occurring germline and tumor-associated mutations within the ATP-binding motifs of PTEN lead to oxidative damage of DNA associated with decreased nuclear p53.

    abstract::Somatic and germline mutations in PTEN (phosphatase and tensin homolog deleted on chromosome 10) are found in sporadic cancers and Cowden syndrome patients, respectively. Recent identification of naturally occurring cancer and germline mutations within the ATP-binding motifs of PTEN (heretofore referred to as PTEN ATP...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddq434

    authors: He X,Ni Y,Wang Y,Romigh T,Eng C

    更新日期:2011-01-01 00:00:00

  • SOX10 regulates an alternative promoter at the Charcot-Marie-Tooth disease locus MTMR2.

    abstract::Schwann cells are the myelinating glia of the peripheral nervous system and dysfunction of these cells causes motor and sensory peripheral neuropathy. The transcription factor SOX10 is critical for Schwann cell development and maintenance, and many SOX10 target genes encode proteins required for Schwann cell function....

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddw233

    authors: Fogarty EA,Brewer MH,Rodriguez-Molina JF,Law WD,Ma KH,Steinberg NM,Svaren J,Antonellis A

    更新日期:2016-09-15 00:00:00

  • Expression of C9orf72-related dipeptides impairs motor function in a vertebrate model.

    abstract::Large expansions of hexanucleotide GGGGCC (G4C2) repeats (hundreds to thousands) in the first intron of the chromosome 9 open reading frame 72 (C9orf72) locus are the strongest known genetic factor associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Different hypotheses exist about the...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddy083

    authors: Swaminathan A,Bouffard M,Liao M,Ryan S,Callister JB,Pickering-Brown SM,Armstrong GAB,Drapeau P

    更新日期:2018-05-15 00:00:00

  • Improved imputation accuracy in Hispanic/Latino populations with larger and more diverse reference panels: applications in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

    abstract::Imputation is commonly used in genome-wide association studies to expand the set of genetic variants available for analysis. Larger and more diverse reference panels, such as the final Phase 3 of the 1000 Genomes Project, hold promise for improving imputation accuracy in genetically diverse populations such as Hispani...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddw174

    authors: Nelson SC,Stilp AM,Papanicolaou GJ,Taylor KD,Rotter JI,Thornton TA,Laurie CC

    更新日期:2016-08-01 00:00:00

  • Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice.

    abstract::Peroxisome proliferator-activated receptors (PPARs) are ligand-mediated transcription factors, which control both lipid and energy metabolism and inflammation pathways. PPARγ agonists are effective in the treatment of metabolic diseases and, more recently, neurodegenerative diseases, in which they show promising neuro...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/dds355

    authors: Dumont M,Stack C,Elipenahli C,Jainuddin S,Gerges M,Starkova N,Calingasan NY,Yang L,Tampellini D,Starkov AA,Chan RB,Di Paolo G,Pujol A,Beal MF

    更新日期:2012-12-01 00:00:00

  • Epigenetic maturation in colonic mucosa continues beyond infancy in mice.

    abstract::Monozygotic twin and other epidemiologic studies indicate that epigenetic processes may play an important role in the pathogenesis of inflammatory bowel diseases that commonly affect the colonic mucosa. The peak onset of these disorders in young adulthood suggests that epigenetic changes normally occurring in the colo...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddq095

    authors: Kellermayer R,Balasa A,Zhang W,Lee S,Mirza S,Chakravarty A,Szigeti R,Laritsky E,Tatevian N,Smith CW,Shen L,Waterland RA

    更新日期:2010-06-01 00:00:00

  • The human RHOX gene cluster: target genes and functional analysis of gene variants in infertile men.

    abstract::The X-linked reproductive homeobox (RHOX) gene cluster encodes transcription factors preferentially expressed in reproductive tissues. This gene cluster has important roles in male fertility based on phenotypic defects of Rhox-mutant mice and the finding that aberrant RHOX promoter methylation is strongly associated w...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddw313

    authors: Borgmann J,Tüttelmann F,Dworniczak B,Röpke A,Song HW,Kliesch S,Wilkinson MF,Laurentino S,Gromoll J

    更新日期:2016-11-15 00:00:00

  • Reduced protein turnover mediates functional deficits in transgenic mice expressing the 25 kDa C-terminal fragment of TDP-43.

    abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP) are two neurodegenerative disorders characterized by the accumulation of TDP-43. TDP-43 is proteolitically cleaved to generate two major C-terminal fragments of 35 and 25 kDa. The latter, known as TDP-25, is a consistent feature of FT...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddv193

    authors: Caccamo A,Shaw DM,Guarino F,Messina A,Walker AW,Oddo S

    更新日期:2015-08-15 00:00:00

  • A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia.

    abstract::The apolipoprotein A5 gene (APOA5 ) has been shown to play an important role in determining plasma triglyceride concentrations in humans. We describe here a novel variant, c.553G>T, in the apolipoprotein A5 gene that is associated with hypertriglyceridemia. In contrast to some other polymorphisms, which occur in non-c...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddg255

    authors: Kao JT,Wen HC,Chien KL,Hsu HC,Lin SW

    更新日期:2003-10-01 00:00:00

  • Interaction between the ligand-binding domain of the LDL receptor and the C-terminal domain of PCSK9 is required for PCSK9 to remain bound to the LDL receptor during endosomal acidification.

    abstract::Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor homology domain repeat A of the low-density lipoprotein receptor (LDLR) at the cell surface and disrupts recycling of the internalized LDLR. As a consequence, the LDLR is rerouted to the lysosomes for degradation. Although PCSK9...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddr578

    authors: Tveten K,Holla ØL,Cameron J,Strøm TB,Berge KE,Laerdahl JK,Leren TP

    更新日期:2012-03-15 00:00:00

  • Hypoxic drive caused type 3 neovascularization in a preclinical model of exudative age-related macular degeneration.

    abstract::Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularizatio...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddz159

    authors: Zhang L,Cui X,Han Y,Park KS,Gao X,Zhang X,Yuan Z,Hu Y,Hsu CW,Li X,Bassuk AG,Mahajan VB,Wang NK,Tsang SH

    更新日期:2019-10-15 00:00:00

  • Functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation.

    abstract::Ataxia oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin, a putative DNA/RNA helicase which shares high homology to the yeast Sen1p protein and has been shown to play a role ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddp278

    authors: Suraweera A,Lim Y,Woods R,Birrell GW,Nasim T,Becherel OJ,Lavin MF

    更新日期:2009-09-15 00:00:00

  • RGS4 mRNA expression in postmortem human cortex is associated with COMT Val158Met genotype and COMT enzyme activity.

    abstract::Linkage, association and postmortem studies have implicated regulator of G-protein signaling 4 (RGS4), which negatively modulates signal transduction at G-protein-coupled receptors, as a candidate schizophrenia susceptibility gene. We compared RGS4 mRNA expression in the dorsolateral prefrontal cortex (DLPFC), between...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddl222

    authors: Lipska BK,Mitkus S,Caruso M,Hyde TM,Chen J,Vakkalanka R,Straub RE,Weinberger DR,Kleinman JE

    更新日期:2006-09-15 00:00:00

  • mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD).

    abstract::Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating mutations of the PRKAR1A tumor suppressor gene that encodes the regulatory subunit R1α of the cAMP-dependent protein kinase (PKA). In human and mouse adrenocortical cells, these mutations lead to increased PKA activity, which resu...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddu265

    authors: de Joussineau C,Sahut-Barnola I,Tissier F,Dumontet T,Drelon C,Batisse-Lignier M,Tauveron I,Pointud JC,Lefrançois-Martinez AM,Stratakis CA,Bertherat J,Val P,Martinez A

    更新日期:2014-10-15 00:00:00

  • Evidence for premature aging due to oxidative stress in iPSCs from Cockayne syndrome.

    abstract::Cockayne syndrome (CS) is a human premature aging disorder associated with neurological and developmental abnormalities, caused by mutations mainly in the CS group B gene (ERCC6). At the molecular level, CS is characterized by a deficiency in the transcription-couple DNA repair pathway. To understand the role of this ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/dds211

    authors: Andrade LN,Nathanson JL,Yeo GW,Menck CF,Muotri AR

    更新日期:2012-09-01 00:00:00