How does the end begin?

Zakian, Virginia A.; Runge, Kurt W.; Wang, Sy Shi

doi:10.1016/0168-9525(90)90043-6

Cited by 55 publications

(8 citation statements)

References 25 publications

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“…Such DNA replication-dependent loss of telomere length seems to be a mitotic clock for counting the number of cell divisions and signaling cellular senescence (73). In our present study, we have shown that the telomere length becomes shortened during division of bovine lens epithelial cells.…”

Section: Modulates Expression Of Pka␣ and Pkc␣ Which Enhances Suppresupporting

confidence: 58%

Human Telomerase Reverse Transcriptase Immortalizes Bovine Lens Epithelial Cells and Suppresses Differentiation through Regulation of the ERK Signaling Pathway

Wang

Feng

Huang

et al. 2005

Journal of Biological Chemistry

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Telomerase is a specialized reverse transcriptase that extends telomeres of eukaryotic chromosomes. The functional telomerase complex contains a telomerase reverse transcriptase catalytic subunit and a telomerase template RNA. We have previously demonstrated that human telomerase reverse transcriptase (hTERT) catalytic subunit is functionally compatible with a telomerase template RNA from rabbit. In this study, we show that hTERT is also functionally compatible with a telomerase template RNA from bovine. Introduction of hTERT into bovine lens epithelial cells (BLECs) provides the transfected cells telomerase activity. The expressed hTERT in BLECs supports normal growth of the transfected cells for 108 population doublings so far, and these cells are still extremely healthy in both morphology and growth. In contrast, the vector-transfected cells display growth crisis after 20 population doublings. These cells run into cellular senescence due to shortening of the telomeres and also commit differentiation as indicated by the accumulation of the differentiation markers, ␤-crystallin and filensin. hTERT prevents the occurrence of both events. By synthesizing new telomere, hTERT prevents replicative senescence, and through regulation of MEK/ERK, protein kinase C, and protein kinase A and eventual suppression of the MEK/ ERK signaling pathway, hTERT inhibits differentiation of BLECs. Our finding that hTERT can suppress RAS/RAF/MEK/ERK signaling pathway to prevent differentiation provides a novel mechanism to explain how hTERT regulates cell differentiation.

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Section: Modulates Expression Of Pka␣ and Pkc␣ Which Enhances Suppresupporting

confidence: 58%

Human Telomerase Reverse Transcriptase Immortalizes Bovine Lens Epithelial Cells and Suppresses Differentiation through Regulation of the ERK Signaling Pathway

Wang

Feng

Huang

et al. 2005

Journal of Biological Chemistry

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“…Here too there are differences in sequence and copy number of repeat units between species and strains of the same species; however, the integral role these structures have in chromosome replication and organization is well established (Zakian et aL, 1990). Other seemingly useless structures such as satellite DNA and heterochromatin have recently been revealed as having defined nuclear functions (Clarke & Baum, 1990).…”

Section: Genome Canalization: Pattern and Processmentioning

confidence: 99%

Genome canalization: the coevolution of transposable and interspersed repetitive elements with single copy DNA

et al. 1992

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Transposable and interspersed repetitive elements (TIREs) are ubiquitous features of both prokaryotic and eukaryotic genomes. However, controversy has arisen as to whether these sequences represent useless 'selfish' DNA elements, with no cellular function, as opposed to useful genetic units. In this review, we selected two insect species, the Dipteran Drosophila and the Lepidopteran Bombyx mori (the silkmoth), in an attempt to resolve this debate. These two species were selected on the basis of the special interest that our laboratory has had over the years in Bombyx with its well known molecular and developmental biology, and the wealth of genetic data that exist for Drosophila. In addition, these two species represent contrasting repetitive element types and patterns of distribution. On one hand, Bombyx exhibits the short interspersion pattern in which Alu-like TIREs predominate while Drosophila possesses the long interspersion pattern in which retroviral-like TIREs are prevalent. In Bombyx, the main TIRE family is Bm-1 while the Drosophila group contains predominantly copia-like elements, non-LTR retroposons, bacterial-type retroposons and fold-back transposable elements sequences. Our analysis of the information revealed highly non-random patterns of both TIRE biology and evolution, more indicative of these sequences acting as genomic symbionts under cellular regulation rather than useless or selfish junk DNA. In addition, we extended our analysis of potential TIRE functionality to what is known from other eukaryotic systems. From this study, it became apparent that these DNA elements may have originated as innocuous or selfish sequences and then adopted functions. The mechanism for this conversion from non-functionality to specific roles is a process of coevolution between the repetitive element and other cellular DNA often times in close physical proximity. The resulting interdependence between repetitive elements and other cellular sequences restrict the number of evolutionarily successful mutational changes for a given function or cistron. This mutual limitation is what we call genome canalization. Well documented examples are discussed to support this hypothesis and a mechanistic model is presented for how such genomic canalization can occur. Also proposed are empirical studies which would support or invalidate aspects of this hypothesis.

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“…They are responsible for preserving chromosome structural integrity and stability, ensuring complete replication of chromosomal termini, and associating chromosomes with the nuclear matrix (Blackburn, 1991;Henderson & Larson, 1991;Price, 1992). Inmostcases, telomeric DNA consists of short repetitive sequences containing a guanine-rich strand running 5' to 3' toward the end of the chromosome and a complementary cytosine-rich strand (Greider, 1991;Zakian et al, 1990). At the very end of the chromosome, the guanine strand forms a 3' overhang of approximately two sequence repeats (Henderson & Blackburn, 1989;Klobutcher et al, 1981;Pluta et al, 1982).…”

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confidence: 99%

G-Wires: Self-Assembly of a Telomeric Oligonucleotide, d(GGGGTTGGGG), into Large Superstructures

Marsh¹,

Henderson²

1994

Biochemistry

159

150

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The telomeric DNA oligonucleotide 5'-G4T2G4-3' (Tet 1.5) spontaneously assembles into large superstructures we have termed G-wires. G-wires can be resolved by gel electrophoresis as a ladder pattern.The self-association of Tet 1.5 is noncovalent and exhibits characteristics of G4-DNA, a parallel fourstranded structure stabilized by guanine tetrads. Formation of G-wires is dependent upon the presence of Na+ and/or K+, and once formed, G-wires are resistant to denaturation. The results described here extend our understanding of the structural potential of G-rich nucleic acids and may provide insight into the * To whom correspondence should be addressed.

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How does the end begin?

Cited by 55 publications

References 25 publications

Human Telomerase Reverse Transcriptase Immortalizes Bovine Lens Epithelial Cells and Suppresses Differentiation through Regulation of the ERK Signaling Pathway

Human Telomerase Reverse Transcriptase Immortalizes Bovine Lens Epithelial Cells and Suppresses Differentiation through Regulation of the ERK Signaling Pathway

Genome canalization: the coevolution of transposable and interspersed repetitive elements with single copy DNA

G-Wires: Self-Assembly of a Telomeric Oligonucleotide, d(GGGGTTGGGG), into Large Superstructures

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