Tetrahymena telomerase catalyzes nucleolytic cleavage and nonprocessive elongation.

Collins, Kathleen; Greider, Carol W.

doi:10.1101/gad.7.7b.1364

Cited by 157 publications

(179 citation statements)

References 33 publications

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“…This model is consistent with the observation that the telomerases of other eukaryotes possess a 3' to 5' exonuclease activity and are capable of elongating non-telomeric primers (33,34,35).…”

Section: Discussionsupporting

confidence: 79%

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum

et al. 1994

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Section: Discussionsupporting

confidence: 79%

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum

et al. 1994

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“…The selected targets may be the result of multiple specificities determined by short sequences that can anneal with TLC1 and possibly contain minimal Cdc13-binding sites (10,31) and Est1 recognition sites. Our data cannot resolve whether broken target DNAs are resected to leave a target sequence at the very end of a 3Ј overhang or whether annealing can occur at internal sequences followed by cleavage by the endonucleolytic activity of telomerase itself (20,32,33); however, only a small percentage target fragments are without TG-rich ends.…”

Section: Discussionmentioning

confidence: 87%

Chromosome healing through terminal deletions generated by de novo telomere additions in Saccharomyces cerevisiae

Putnam

Pennaneach

Kolodner

2004

Proc. Natl. Acad. Sci. U.S.A.

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Broken chromosomes healed by de novo addition of a telomere are a major class of genome rearrangements seen in Saccharomyces cerevisiae and similar to rearrangements seen in human tumors. We have analyzed the sequences of 534 independent de novo telomere additions within a 12-kb region of chromosome V. The distribution of events mirrored that of four-base sequences consisting of the GG, GT, and TG dinucleotides, suggesting that de novo telomere additions occur at short regions of homology to the telomerase guide RNA. These chromosomal sequences restrict potential registrations of the added telomere sequence. The first 11 nucleotides of the addition sequences fell into common families that included 91% of the breakpoints. The observed registrations suggest that the 3 end of the TLC1 guide RNA is involved in annealing but not as a template for synthesis. Some families of added sequences can be accounted for by one cycle of annealing and extension, whereas others require a minimum of two. The same pattern emerges for sequences added onto the most common addition sequence, indicating that de novo telomeres are added and extended by the same process. Together, these data indicate that annealing is central to telomerase registration, which limits telomere heterogeneity and resolves the problem of synthesizing Rap1 binding sites by a nonprocessive telomerase with a lowcomplexity guide RNA sequence.

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“…Both the RNA template and some putative DNA-binding domain(s) of the telomerase protein are thought to contribute to this preference (32)(33)(34)(35). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Telomerase can act as a template- and RNA-independent terminal transferase

Lue

Bosoy

Moriarty

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Telomerase is a special reverse transcriptase that extends one strand of the telomere repeat by using a template embedded in an RNA subunit. Like other polymerases, telomerase is believed to use a pair of divalent metal ions (coordinated by a triad of aspartic acid residues) for catalyzing nucleotide addition. Here we show that, in the presence of manganese, both yeast and human telomerase can switch to a template-and RNA-independent mode of DNA synthesis, acting in effect as a terminal transferase. Even as a terminal transferase, yeast telomerase retains a species-dependent preference for GT-rich, telomere-like DNA on the 5 end of the substrate. The terminal transferase activity of telomerase may account for some of the hitherto unexplained effects of telomerase overexpression on cell physiology.reverse transcriptase ͉ telomere ͉ divalent metal ion T elomerase is a ribonucleoprotein responsible for the synthesis of one strand of the telomere terminal repeat. The catalytic core of telomerase consists minimally of two components: an RNA in which the template is embedded (named TLC1 in the budding yeast Saccharomyces cerevisiae), and a reverse transcriptase (RT)-like protein that mediates catalysis (named TERT in general and Est2p in yeast) (1-4). Telomerase RNAs from different organisms are divergent in sequence but share conserved secondary structural elements (5, 6). Many mutations in nontemplate regions of telomerase RNA reduced enzyme activity, suggesting that these regions contribute important catalytic functions [although the precise nature of the contribution(s) is not clear] (7-9). Other RNA structures act to define the boundary of the template segment that supports reverse transcription (10, 11). Thus, the RNA subunit serves multiple essential roles in the course of a normal telomerase reaction. The TERT protein is well conserved in evolution and comprises a central RT domain that is flanked on both the N-and C-terminal side by telomerase-specific motifs (4, 12, 13). Mutational analysis indicates that these motifs are likely to mediate binding to telomeric DNA and telomerase RNA. Direct recognition of telomeric DNA by TERT is believed to be sequence-dependent and to allow telomerase to catalyze the addition of multiple repeats without dissociation from the DNA (13,14).In unicellular organisms, telomerase is constitutively active and required for the long-term proliferation of cells. In some multicellular organisms, including humans, telomerase is repressed in normal somatic tissues but activated in cancer cells, and is believed to promote tumor growth (15). Although the two core components of telomerase are generally assumed to act in concert to replenish telomeres, there is increasing evidence that the TERT protein can have physiologic effects that are independent of telomere length and telomerase . For instance, in mice, TERT overexpression in the absence of telomerase RNA was reported to have an inhibitory effect on tumorigenesis and wound healing (20). The mechanisms for such effects are currently no...

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Tetrahymena telomerase catalyzes nucleolytic cleavage and nonprocessive elongation.

Cited by 157 publications

References 33 publications

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum

Chromosome healing through terminal deletions generated by de novo telomere additions in Saccharomyces cerevisiae

Telomerase can act as a template- and RNA-independent terminal transferase

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