<i>TLC1</i>
            : Template RNA Component of
            <i>Saccharomyces cerevisiae</i>
            Telomerase

Singer, M; Gottschling, Daniel E.

doi:10.1126/science.7545955

Cited by 711 publications

(720 citation statements)

References 54 publications

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“…Telomeres consist of lengthy G-rich simple repeat sequences that are synthesized de novo by a specialized reverse transcriptase known as telomerase (Greider and Blackburn, 1985;Yu et al, 1990;Singer and Gottschling, 1994). The telomerase core enzyme consists of an RNA component and a polypeptide that bears classical structural motifs and functional activities of a reverse transcriptase Nakamura et al, 1997Nakamura et al, , 1998Meyerson et al, 1997;Harrington et al, 1997;Kilian et al, 1997;.…”

Section: Introductionmentioning

confidence: 99%

Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation

et al. 1998

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We have identi®ed the mouse telomerase reverse transcriptase component (mTERT) and demonstrate both substantial sequence homology to the human ortholog (hTERT), and the presence of reverse transcriptase and telomerase speci®c motifs. Furthermore, we show functional interchangeability with hTERT in in vitro telomerase reconstitution experiments, as mTERT produces strong telomerase activity in combination with the human telomerase RNA component hTR. The mouse TERT is widely expressed at low levels in adult tissues, with greatest abundance during embryogenesis and in adult thymus and intestine. The mTERT component mRNA levels were regulated during both di erentiation and proliferation, while mTR levels remained constant throughout both processes. Comparison of mTERT and mTR levels to telomerase activity indicates that mTERT expression is more tightly linked to the regulation of telomerase activity during these processes than is mTR. In contrast to the situation in human cell cultures, mTERT transcript levels are present at readily detectable levels in primary cultured cells and are not upregulated following crisis. The widespread expression of mTERT in primary cells and mouse tissues could explain the increased frequency of spontaneous immortalization of mouse cells in culture and tumorigenesis in vivo.

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Section: Introductionmentioning

confidence: 99%

Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation

et al. 1998

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“…The RNA component of telomerase provides the template for de novo telomere repeat synthesis. The RNA component has been cloned and characterized in ciliates, yeast, humans and mice (Blackburn, 1992;Zakian, 1995;Feng et al, 1995;Blasco et al, 1995;Singer and Gollschling, 1994;Gilley and Blackburn, 1996). Telomeres protect chromosomes from DNA degradation, end-to-end fusions, and rearrangements (McClintock, 1941;Blackburn, 1991;Zakian, 1995).…”

Section: Introductionmentioning

confidence: 99%

Expression of telomerase in normal and malignant rat hepatic epithelia

et al. 1997

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“…Sequence patterns can be summarized with the consensus sequence {(TG) 0-6 TGGGTGTG(G) n } (39). This heterogeneity can be understood by examining the features of the unusually large telomerase RNA templating sequence, (here 3'-5') ACACACACCCACACCAC (41). The variability observed of yeast telomeres can be completely explained by a combination of abortive reverse transcription of this template and the ability of the template to bind substrate in more than one register (39).…”

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Identification of the Determinants for the Specific Recognition of Single-Strand Telomeric DNA by Cdc13

2005

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The single-strand overhang present at all known telomeres plays a critical role in mediating both the capping and telomerase regulation functions of telomeres. The telomere end-binding proteins, Cdc13 in S. cerevisiae, Pot1 in higher eukaryotes, and TEBP in the ciliated protozoa O. nova, exhibit sequence-specific binding to their respective single-strand overhangs. S. cerevisiae telomeres are composed of a heterogeneous mixture of GT-rich telomeric sequence, unlike in higher eukaryotes which have a simple repeat that is maintained with high fidelity. In yeast, the telomeric overhang is recognized by the essential protein Cdc13, which coordinates end-capping and telomerase activities at the telomere. The Cdc13-DNA-binding domain (Cdc13-DBD) binds these telomere sequences with high affinity (3 pM) and sequence specificity. To better understand the basis for this remarkable recognition, we have investigated the binding of the Cdc13-DBD to a series of altered DNA substrates. Although an 11-mer of GT-rich sequence is required for full binding affinity, only 3 of these 11 bases are recognized with high specificity. This specificity differs from that observed in the other known telomere end-binding proteins, but is well suited to the specific role of Cdc13 at yeast telomeres. These studies expand our understanding of telomere recognition by the Cdc13-DBD and of the unique molecular recognition properties of ssDNA binding.Recognition of single-strand DNA (ssDNA) is essential for many fundamental cellular activities, including recombination, repair, replication, transcription, translation, and telomere maintenance. Structural and biochemical studies of the proteins that mediate ssDNA-binding activity have provided key insights into the mechanism of recognition. Generally, small domains containing mixed α/β topologies, such as the OB-fold and KH domain, are used for ssDNA recognition, and binding is achieved through base and backbone interactions that are completely distinct from those used in double-strand DNA recognition (1-5). In many biological contexts DNA needs to be uniformly recognized, thus it is appropriate for this recognition to be non-sequence specific. However, in a few cases, including telomere maintenance, transcription, and viral packaging, it is imperative that recognition be exquisitely sequence specific (3,(6)(7)(8).Telomeres, the DNA, RNA and protein complexes at the ends of chromosomes, play important roles in many essential cellular functions. They regulate the proliferative lifetime of the cell and protect chromosomes from degradation or end-to-end fusion, as well as participate in meiotic segregation and chromatic silencing (reviewed in (9-13)). Telomeres are critical to the maintenance of the genome and normal development. Thus, telomere malfunction can have dramatic adverse impacts on human health, leading to cancer, aging disorders and increased human mortality (14)(15)(16)(17)(18)(19). Therefore, it is essential to understand the mechanisms through which telomeres are properly maintain...

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TLC1 : Template RNA Component of Saccharomyces cerevisiae Telomerase

Cited by 711 publications

References 54 publications

Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation

Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation

Expression of telomerase in normal and malignant rat hepatic epithelia

Identification of the Determinants for the Specific Recognition of Single-Strand Telomeric DNA by Cdc13

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