GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Normal human chromosomes have long G-rich telomeric overhangs at one end
    Cold Spring Harbor Laboratory ; 1997
    In:  Genes & Development Vol. 11, No. 21 ( 1997-11-01), p. 2801-2809
    Details
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 11, No. 21 ( 1997-11-01), p. 2801-2809
    Abstract: Telomeres protect the ends of linear chromosomes from degradation and abnormal recombination events, and in vertebrates may be important in cellular senescence and cancer. However, very little is known about the structure of human telomeres. In this report we purify telomeres and analyze their termini. We show that following replication the daughter telomeres have different terminal overhangs in normal diploid telomerase-negative human fibroblasts. Electron microscopy of those telomeres that have long overhangs yields 200 ± 75 nucleotides of single-stranded DNA. This overhang is four times greater than the amount of telomere shortening per division found in these cells. These results are consistent with models of telomere replication in which leading-strand synthesis generates a blunt end while lagging-strand synthesis produces a long G-rich 3′ overhang, and suggest that variations in lagging-strand synthesis may regulate the rate of telomere shortening in normal diploid human cells. Our results do not exclude the possibility that nuclease processing events following leading strand synthesis result in short overhangs on one end.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    URL: Article
    DOI: 10.1101/gad.11.21.2801
    RVK:
    WA 15000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 1997
    detail.hit.zdb_id: 1467414-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    MYC promotes tryptophan uptake and metabolism by the kynurenine pathway in colon cancer
    Cold Spring Harbor Laboratory ; 2019
    In:  Genes & Development Vol. 33, No. 17-18 ( 2019-09-01), p. 1236-1251
    Details
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 33, No. 17-18 ( 2019-09-01), p. 1236-1251
    Abstract: Tumors display increased uptake and processing of nutrients to fulfill the demands of rapidly proliferating cancer cells. Seminal studies have shown that the proto-oncogene MYC promotes metabolic reprogramming by altering glutamine uptake and metabolism in cancer cells. How MYC regulates the metabolism of other amino acids in cancer is not fully understood. Using high-performance liquid chromatography (HPLC)-tandem mass spectrometry (LC-MS/MS), we found that MYC increased intracellular levels of tryptophan and tryptophan metabolites in the kynurenine pathway. MYC induced the expression of the tryptophan transporters SLC7A5 and SLC1A5 and the enzyme arylformamidase (AFMID), involved in the conversion of tryptophan into kynurenine. SLC7A5, SLC1A5, and AFMID were elevated in colon cancer cells and tissues, and kynurenine was significantly greater in tumor samples than in the respective adjacent normal tissue from patients with colon cancer. Compared with normal human colonic epithelial cells, colon cancer cells were more sensitive to the depletion of tryptophan. Blocking enzymes in the kynurenine pathway caused preferential death of established colon cancer cells and transformed colonic organoids. We found that only kynurenine and no other tryptophan metabolite promotes the nuclear translocation of the transcription factor aryl hydrocarbon receptor (AHR). Blocking the interaction between AHR and kynurenine with CH223191 reduced the proliferation of colon cancer cells. Therefore, we propose that limiting cellular kynurenine or its downstream targets could present a new strategy to reduce the proliferation of MYC-dependent cancer cells.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    URL: Article
    DOI: 10.1101/gad.327056.119
    RVK:
    WA 15000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2019
    detail.hit.zdb_id: 1467414-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions
    Cold Spring Harbor Laboratory ; 2001
    In:  Genes & Development Vol. 15, No. 4 ( 2001-02-15), p. 398-403
    Details
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 15, No. 4 ( 2001-02-15), p. 398-403
    Abstract: Telomere shortening is the mechanism underlying replicative aging in fibroblasts. A variety of reports now claim that inactivation of the p16 INK4a /pRB pathway is required in addition to telomere maintenance for the immortalization of cells such as skin keratinocytes and breast epithelial cells. We here show that the premature growth arrest of these cell types can be explained by an inadequate culture environment. Providing mesenchymal/epithelial interactions by cultivating the telomerase-expressing cells on feeder layers avoids the growth arrest associated with increased p16 INK4a . These results do not support a telomere-independent mechanism of replicative aging.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    URL: Article
    DOI: 10.1101/gad.859201
    RVK:
    WA 15000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2001
    detail.hit.zdb_id: 1467414-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    SORBS2 transcription is activated by telomere position effect–over long distance upon telomere shortening in muscle cells from patients with facioscapulohumeral dystrophy
    Cold Spring Harbor Laboratory ; 2015
    In:  Genome Research Vol. 25, No. 12 ( 2015-12), p. 1781-1790
    Details
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 25, No. 12 ( 2015-12), p. 1781-1790
    Abstract: DNA is organized into complex three-dimensional chromatin structures, but how this spatial organization regulates gene expression remains a central question. These DNA/chromatin looping structures can range in size from 10–20 kb (enhancers/repressors) to many megabases during intra- and inter-chromosomal interactions. Recently, the influence of telomere length on chromatin organization prior to senescence has revealed the existence of long-distance chromatin loops that dictate the expression of genes located up to 10 Mb from the telomeres (Telomere Position Effect–Over Long Distances [TPE-OLD]). Here, we demonstrate the existence of a telomere loop at the 4q35 locus involving the sorbin and SH3 domain-containing protein 2 gene, SORBS2 , a skeletal muscle protein using a modification of the chromosome conformation capture method. The loop reveals a cis -acting mechanism modifying SORBS2 transcription. The expression of this gene is altered by TPE-OLD in myoblasts from patients affected with the age-associated genetic disease, facioscapulohumeral muscular dystrophy (FSHD1A, MIM 158900). SORBS2 is expressed in FSHD myoblasts with short telomeres, while not detectable in FSHD myoblasts with long telomeres or in healthy myoblasts regardless of telomere length. This indicates that TPE-OLD may modify the regulation of the 4q35 locus in a pathogenic context. Upon differentiation, both FSHD and healthy myotubes express SORBS2 , suggesting that SORBS2 is normally up-regulated by maturation/differentiation of skeletal muscle and is misregulated by TPE-OLD-dependent variegation in FSHD myoblasts. These findings provide additional insights for the complexity and age-related symptoms of FSHD.
    Type of Medium: Online Resource
    ISSN: 1088-9051 , 1549-5469
    URL: Article
    DOI: 10.1101/gr.190660.115
    RVK:
    XA 10000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2015
    detail.hit.zdb_id: 1483456-X
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Clustered telomeres in phase-separated nuclear condensates engage mitotic DNA synthesis through BLM and RAD52
    Cold Spring Harbor Laboratory ; 2019
    In:  Genes & Development Vol. 33, No. 13-14 ( 2019-07-01), p. 814-827
    Details
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 33, No. 13-14 ( 2019-07-01), p. 814-827
    Abstract: Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism that occurs in a subset of cancers. One of the hallmarks of ALT cancer is the excessively clustered telomeres in promyelocytic leukemia (PML) bodies, represented as large bright telomere foci. Here, we present a model system that generates telomere clustering in nuclear polySUMO (small ubiquitin-like modification)/polySIM (SUMO-interacting motif) condensates, analogous to PML bodies, and thus artificially engineered ALT-associated PML body (APB)-like condensates in vivo. We observed that the ALT-like phenotypes (i.e., a small fraction of heterogeneous telomere lengths and formation of C circles) are rapidly induced by introducing the APB-like condensates together with BLM through its helicase domain, accompanied by ssDNA generation and RPA accumulation at telomeres. Moreover, these events lead to mitotic DNA synthesis (MiDAS) at telomeres mediated by RAD52 through its highly conserved N-terminal domain. We propose that the clustering of large amounts of telomeres in human cancers promotes ALT that is mediated by MiDAS, analogous to Saccharomyces cerevisiae type II ALT survivors.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    URL: Article
    DOI: 10.1101/gad.324905.119
    RVK:
    WA 15000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2019
    detail.hit.zdb_id: 1467414-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    The La antigen associates with the human telomerase ribonucleoprotein and influences telomere length in vivo
    Cold Spring Harbor Laboratory ; 2001
    In:  RNA Vol. 7, No. 8 ( 2001-8), p. 1068-1075
    Details
    In: RNA, Cold Spring Harbor Laboratory, Vol. 7, No. 8 ( 2001-8), p. 1068-1075
    Type of Medium: Online Resource
    ISSN: 1355-8382
    URL: Article
    DOI: 10.1017/S1355838201010159
    Language: Unknown
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2001
    detail.hit.zdb_id: 1475737-0
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    The aryl hydrocarbon receptor regulates nucleolar activity and protein synthesis in MYC-expressing cells
    Cold Spring Harbor Laboratory ; 2018
    In:  Genes & Development Vol. 32, No. 19-20 ( 2018-10-01), p. 1303-1308
    Details
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 32, No. 19-20 ( 2018-10-01), p. 1303-1308
    Abstract: MYC enhances protein synthesis by regulating genes involved in ribosome biogenesis and protein translation. Here, we show that MYC-induced protein translation is mediated by the transcription factor aryl hydrocarbon receptor (AHR), which is induced by MYC in colonic cells. AHR promotes protein synthesis by activating the transcription of genes required for ribosome biogenesis and protein translation, including OGFOD1 and NOLC1. Using surface sensing of translation (SUnSET) to measure global protein translation, we found that silencing AHR or its targets diminishes protein synthesis. Therefore, targeting AHR or its downstream pathways could provide a novel approach to limit biomass production in MYC-driven tumors.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    URL: Article
    DOI: 10.1101/gad.313007.118
    RVK:
    WA 15000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2018
    detail.hit.zdb_id: 1467414-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Telomere position effect: regulation of gene expression with progressive telomere shortening over long distances
    Cold Spring Harbor Laboratory ; 2014
    In:  Genes & Development Vol. 28, No. 22 ( 2014-11-15), p. 2464-2476
    Details
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 28, No. 22 ( 2014-11-15), p. 2464-2476
    Abstract: While global chromatin conformation studies are emerging, very little is known about the chromatin conformation of human telomeres. Most studies have focused on the role of telomeres as a tumor suppressor mechanism. Here we describe how telomere length regulates gene expression long before telomeres become short enough to produce a DNA damage response (senescence). We directly mapped the interactions adjacent to specific telomere ends using a Hi-C (chromosome capture followed by high-throughput sequencing) technique modified to enrich for specific genomic regions. We demonstrate that chromosome looping brings the telomere close to genes up to 10 Mb away from the telomere when telomeres are long and that the same loci become separated when telomeres are short. Furthermore, expression array analysis reveals that many loci, including noncoding RNAs, may be regulated by telomere length. We report three genes (ISG15 [interferon-stimulated gene 15 kd], DSP [Desmoplakin] , and C1S [complement component 1s subcomplement]) located at three different subtelomeric ends (1p, 6p, and 12p) whose expressions are altered with telomere length. Additionally, we confirmed by in situ analysis (3D-FISH [three-dimensional fluorescence in situ hybridization] ) that chromosomal looping occurs between the loci of those genes and their respective telomere ends. We term this process TPE-OLD for “telomere position effect over long distances.” Our results suggest a potential novel mechanism for how telomere shortening could contribute to aging and disease initiation/progression in human cells long before the induction of a critical DNA damage response.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    URL: Article
    DOI: 10.1101/gad.251041.114
    RVK:
    WA 15000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2014
    detail.hit.zdb_id: 1467414-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Early and late steps in telomere overhang processing in normal human cells: the position of the final RNA primer drives telomere shortening
    Cold Spring Harbor Laboratory ; 2012
    In:  Genes & Development Vol. 26, No. 11 ( 2012-06-01), p. 1167-1178
    Details
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 26, No. 11 ( 2012-06-01), p. 1167-1178
    Abstract: Telomere overhangs are essential for telomere end protection and telomerase extension, but how telomere overhangs are generated is unknown. Leading daughter strands synthesized by conventional semiconservation DNA replication are initially blunt, while lagging daughter strands are shorter by at least the size of the final RNA primer, which is thought to be located at extreme chromosome ends. We developed a variety of new approaches to define the steps in the processing of these overhangs. We show that the final lagging RNA primer is not terminal but is randomly positioned ∼70–100 nucleotides from the ends and is not removed for more than an hour. This identifies an important intrinsic step in replicative aging. Telomeric termini are processed in two distinct phases. During the early phase, which occupies 1–2 h following replication of the duplex telomeric DNA, several steps occur on both leading and lagging daughters. Leading telomere processing remains incomplete until late S/G2, when the C-terminal nucleotide is specified—referred to as the late phase. These observations suggest the presence of previously unsuspected complexes and signaling events required for the replication of the ends of human chromosomes.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    URL: Article
    DOI: 10.1101/gad.187211.112
    RVK:
    WA 15000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2012
    detail.hit.zdb_id: 1467414-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single-cell resolution
    Cold Spring Harbor Laboratory ; 2019
    In:  Genome Research Vol. 29, No. 11 ( 2019-11), p. 1878-1888
    Details
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 29, No. 11 ( 2019-11), p. 1878-1888
    Abstract: Mitochondria are involved in a number of diverse cellular functions, including energy production, metabolic regulation, apoptosis, calcium homeostasis, cell proliferation, and motility, as well as free radical generation. Mitochondrial DNA (mtDNA) is present at hundreds to thousands of copies per cell in a tissue-specific manner. mtDNA copy number also varies during aging and disease progression and therefore might be considered as a biomarker that mirrors alterations within the human body. Here, we present a new quantitative, highly sensitive droplet digital PCR (ddPCR) method, droplet digital mitochondrial DNA measurement (ddMDM), to measure mtDNA copy number not only from cell populations but also from single cells. Our developed assay can generate data in as little as 3 h, is optimized for 96-well plates, and also allows the direct use of cell lysates without the need for DNA purification or nuclear reference genes. We show that ddMDM is able to detect differences between samples whose mtDNA copy number was close enough as to be indistinguishable by other commonly used mtDNA quantitation methods. By utilizing ddMDM, we show quantitative changes in mtDNA content per cell across a wide variety of physiological contexts including cancer progression, cell cycle progression, human T cell activation, and human aging.
    Type of Medium: Online Resource
    ISSN: 1088-9051 , 1549-5469
    URL: Article
    DOI: 10.1101/gr.250480.119
    RVK:
    XA 10000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2019
    detail.hit.zdb_id: 1483456-X
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...