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  • Articles  (28)
  • Letters, Sustainability Science  (14)
  • Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature  (14)
  • National Academy of Sciences  (28)
  • American Chemical Society
  • American Institute of Physics
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  • Articles  (28)
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  • National Academy of Sciences  (28)
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  • 1
    Publication Date: 2011-06-08
    Description: Romero and Agrawal (1) question the usefulness of our framework to link functional diversity with social actor strategies (2), arguing that it oversimplifies the complexity of the social dimensions of socioecological systems. We agree on the crucial importance of such dimensions, and we repeatedly highlighted this in our article, as is obvious from figure 1, the text, and the examples. While focusing on functional diversity, ecosystem services, and their role in different social actor strategies, we situated these in a broader setting that can be analyzed with the tools and concepts of social sciences, including institutional analyses.Rather than replacing major...
    Keywords: Letters, Sustainability Science
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  • 2
    Publication Date: 2011-06-22
    Description: Essl et al. (1) tested whether historical socioeconomic conditions have created an invasion debt in Europe (i.e., a suite of nonnative species that have not yet been discovered but whose establishment has been determined by previous socioeconomic conditions). Essl et al. (1) tested this theory by asking whether the cumulative numbers of nonnative species presently established in 28 European countries were more closely correlated to socioeconomic conditions in the year 1900 or 2000. In this letter, we describe a flaw in their logic that biases the analysis to concluding that an invasion debt does occur.Essl et al. (1) modeled the...
    Keywords: Letters, Sustainability Science
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  • 3
    Publication Date: 2011-06-22
    Description: Success of the emerging Low Emissions Development paradigm in Southeast Asia depends on mitigating impacts of oil palm (OP) expansion on carbon-dense ecosystems, especially tropical peatlands. To this end, Koh et al. (1) mapped OP planted before 2002 across Peninsular Malaysia, Sumatra, and Borneo to estimate emissions and biodiversity losses from peatland conversion (≈880,000 ha). Unfortunately, emissions scenarios are oversimplified, remote-sensing (RS) methods are unsuitable for OP monitoring, and recommendations for peatland restoration are overstated.The article risks misinforming national and international climate change policies under development.Koh et al. overestimated emissions from aboveground biomass (AGB) conversion to OP (136 million MgC)...
    Keywords: Letters, Sustainability Science
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  • 4
    Publication Date: 2011-06-08
    Description: Díaz et al. (1) proposed an “interdisciplinary framework for the analysis of relationships between functional diversity, ecosystem services, and human actions.” Their framework addresses the linkages between land uses and ecosystem service (ES) provision to inform decisions by relevant parties. We welcome the development and practical application of tools for analyzing the complexity of social-ecological systems (SESs), but there are fundamental gaps in the oversimplified framework of Díaz et al. (1). These flaws obscure critical aspects of the functioning of SESs, preclude their improved understanding, and thereby undermine the goal of fruitful scientific analysis.In particular, the proposed local-level framework does...
    Keywords: Letters, Sustainability Science
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  • 5
    Publication Date: 2011-06-22
    Description: Paoli et al. (1) raise some interesting criticisms of our article (2), but we think that they misinterpret important elements of our study, ignore our consideration of model uncertainties, and fail to recognize the wider significance of our work.We presented a framework for quantifying the impacts of oil-palm expansion on biodiversity and carbon stocks. We did so by combining a unique remote-sensing methodology with a unique species-area model and recently published carbon flux estimates. We also explicitly accounted for and presented uncertainties in all model projections. We estimated that the conversion of peatswamp forests to large-scale, closed canopy oil-palm plantations...
    Keywords: Letters, Sustainability Science
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  • 6
    Publication Date: 2011-06-22
    Description: We recently showed (1) that, for a wide range of taxa, the current numbers of established alien species in 28 European countries were generally more closely related to socioeconomic indicators from the year 1900 than 2000. Thus, the establishment of alien species seemed to lag considerably behind one of the main drivers of alien species introductions (2). We concluded that current high socioeconomic activity could result in considerable additional accumulation of alien species in the future, a phenomenon that we have called invasion debt.Keller and Springborn (3) suggest that cumulative numbers of established alien species would be better explained by...
    Keywords: Letters, Sustainability Science
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  • 7
    Publication Date: 2011-10-05
    Description: Reconstructions and observations of relative sea level (RSL) must be corrected for vertical land movements from glacial isostatic adjustment (GIA) to facilitate comparisons among regions and identify deviations from background rates. Late Holocene (past 2 ka) GIA rates are estimated from geological data and permanent global positioning system (GPS) stations or predicted from GIA models. We used a linear trend fitted to the regional, compaction-free, RSL reconstructions compiled by Engelhart et al. (1) for the past 2 ka (excluding data since AD 1900) as a GIA estimate. Similarly, GIA models also attribute all RSL changes during the past 2 ka...
    Keywords: Letters, Sustainability Science
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  • 8
    Publication Date: 2011-10-05
    Description: Kemp et al. (1) presented a new salt-marsh proxy record of relative sea level (RSL) from North Carolina (NCRSL). The salt marsh is slowly subsiding as a result of glacial isostatic adjustment (GIA), and the NCRSL record needs to be adjusted to remove this vertical land movement from the sea level record. Kemp et al. (1) corrected for a constant subsidence rate of approximately 1 mm/y. This is a “geologic” estimate based on sea level index points, which are determined from linear fits to data from other North American RSL proxy records. Thus, the geologic method implicitly assumes that the...
    Keywords: Letters, Sustainability Science
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  • 9
    Publication Date: 2011-03-02
    Description: West et al.’s recent paper (1) compared tradeoffs of carbon and crop production in temperate and tropical zones. We welcome the empirical evidence in support of agricultural intensification rather than extensification. We strongly caution against the implicit conclusion that food production might need to be concentrated in the temperate zone, however. First, this has implications for food security. People vulnerable to food insecurity live largely in low-income tropical countries and depend predominantly on local agriculture both for food supplies and to provide the livelihoods that underpin food security (2). Second, as the maps of West et al. (1) show, there...
    Keywords: Letters, Sustainability Science
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  • 10
    Publication Date: 2011-03-02
    Description: Vermeulen and Wollenberg (1) caution against interpreting our recent paper (2) as a call to concentrate food production in temperate areas. We did not intend our research to be interpreted as such. As Vermeulen and Wollenberg state, even very low yields can play an extremely important role in providing food security, particularly in low-income tropical countries. We agree that it is important to make the distinction between yields and food security.As noted in our paper, the tradeoff between carbon and crop yields that results from expanding croplands is particularly strong in the tropics, where natural ecosystems generally store a lot...
    Keywords: Letters, Sustainability Science
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  • 11
    Publication Date: 2011-02-23
    Description: Both our study (1) and the follow-up described by Frederick et al. (2) indicate that people know relatively little about how much energy is used by different devices and appliances. In our view, the additional data strengthen rather than weaken our original conclusions.It is well known that numerical judgments are subject to anchoring effects, with initial values having substantial influence on final answers (3). In our article, we noted that the compressed range of respondents’ energy estimates “almost certainly resulted from an anchoring bias in which the reference point provided in the task served as an anchor for participants’ estimates,...
    Keywords: Letters, Sustainability Science
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  • 12
    Publication Date: 2011-02-23
    Description: The adoption of energy-saving technologies is presumably deterred by underestimates of energy use and by corresponding underestimates of the difference between more- and less-efficient appliances. Thus, it is easy to grasp the potential policy significance of a recent study (1) concluding that Americans underestimate energy use by a factor of 2.8.However, the apparent precision of that statistic belies its arbitrary origins. By manipulating just two experimental details (the provided numeric referent and the units in which judgments were rendered), we show that one can readily reach qualitatively different conclusions.For the study in question (1), respondents were first told that a...
    Keywords: Letters, Sustainability Science
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  • 13
    Publication Date: 2011-03-23
    Description: Enhanced weathering of olivine as a means of sequestering carbon is investigated by Köhler et al. (1). Specifically, the study discusses the potential distribution of fine olivine powder, obtained from dunite mines, in the humid tropic regions of the Amazon and Congo River catchments. Olivine (forsterite) dissolution (Eq. 1) implies the sequestration of 4 moles of CO2 for each mole of olivine (2).Köhler et al. (1) suggested that the saturation of silicic acid (H4SiO4) in river runoff would crucially limit olivine dissolution. As an example of the weathering of pulverized ultramafic rock, Wilson et al. (3) present evidence that the...
    Keywords: Letters, Sustainability Science
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  • 14
    Publication Date: 2011-03-23
    Description: Schuiling et al. (1) question our conclusion (2) that the annual dissolution rate of olivine is limited by the saturation of waters with silicic acid (H4SiO4), which is one product of the dissolution reaction of olivine. In support of this point they discuss findings of CO2 sequestration in a mine in Yukon, Canada, claiming that a minimum of 1,700 g C m−2 y−1 was sequestered between 1978 and 2004 by silicate weathering and precipitation of (mainly) magnesium carbonates (3). This value is approximately 20 times larger than the 85 g C m−2 y−1 calculated in our study for the Amazon...
    Keywords: Letters, Sustainability Science
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  • 15
    Publication Date: 2011-12-21
    Description: Telomerase is a unique reverse transcriptase that catalyzes the addition of telomere DNA repeats onto the 3′ ends of linear chromosomes and plays a critical role in maintaining genome stability. Unlike other reverse transcriptases, telomerase is unique in that it is a ribonucleoprotein complex, where the RNA component [telomerase RNA (TR)] not only provides the template for the synthesis of telomere DNA repeats but also plays essential roles in catalysis, accumulation, TR 3′-end processing, localization, and holoenzyme assembly. Biochemical studies have identified TR elements essential for catalysis that share remarkably conserved secondary structures across different species as well as species-specific domains for other functions, paving the way for high-resolution structure determination of TRs. Over the past decade, structures of key elements from the core, conserved regions 4 and 5, and small Cajal body specific RNA domains of human TR have emerged, providing significant insights into the roles of these RNA elements in telomerase function. Structures of all helical elements of the core domain have been recently reported, providing the basis for a high-resolution model of the complete core domain. We review this progress to determine the overall architecture of human telomerase RNA.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 16
    Publication Date: 2011-12-21
    Description: Recent work has identified a subset of cells resident in tumors that exhibit properties similar to those found in normal stem cells. Such cells are highly tumorigenic and may be involved in resistance to treatment. However, the genes that regulate the tumor initiating cell (TIC) state are unknown. Here, we show that overexpression of either of the nucleolar GTP-binding proteins nucleostemin (NS) or GNL3L drives the fraction of genetically defined tumor cells that exhibit markers and tumorigenic properties of TICs. Specifically, cells that constitutively express elevated levels of NS or GNL3L exhibit increased TWIST expression, phosphorylation of STAT3, expression of genes that induce pluripotent stem cells, and enhanced radioresistance; in addition, they form tumors even when small numbers of cells are implanted and exhibit an increased propensity to metastasize. GNL3L/NS forms a complex with the telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] and the SWItch-Sucrose NonFermentable (SWI-SNF) complex protein brahma-related gene 1 (BRG1), and the expression of each of these components is necessary to facilitate the cancer stem cell state. Together, these observations define a complex composed of TERT, BRG1, and NS/GNL3L that maintains the function of TICs.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 17
    Publication Date: 2011-12-21
    Description: Integration sites for many retrotransposons and retroviruses are determined by interactions between retroelement-encoded integrases and specific DNA-bound proteins. The Saccharomyces retrotransposon Ty5 preferentially integrates into heterochromatin because of interactions between Ty5 integrase and the heterochromatin protein silent information regulator 4. We mapped over 14,000 Ty5 insertions onto the S. cerevisiae genome, 76% of which occurred in heterochromatin, which is consistent with the known target site bias of Ty5. Using logistic regression, associations were assessed between Ty5 insertions and various chromosomal features such as genome-wide distributions of nucleosomes and histone modifications. Sites of Ty5 insertion, regardless of whether they occurred in heterochromatin or euchromatin, were strongly associated with DNase hypersensitive, nucleosome-free regions flanking genes. Our data support a model wherein silent information regulator 4 tethers the Ty5 integration machinery to domains of heterochromatin, and then, specific target sites are selected based on DNA access, resulting in a secondary target site bias. For insertions in euchromatin, DNA access is the primary determinant of target site choice. One consequence of the secondary target site bias of Ty5 is that insertions in coding sequences occur infrequently, which may preserve genome integrity.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 18
    Publication Date: 2011-12-21
    Description: Long interspersed element-1 (LINE-1 or L1) retrotransposons encode two proteins (ORF1p and ORF2p) that contain activities required for conventional retrotransposition by a mechanism termed target-site primed reverse transcription. Previous experiments in XRCC4 or DNA protein kinase catalytic subunit-deficient CHO cell lines, which are defective for the nonhomologous end-joining DNA repair pathway, revealed an alternative endonuclease-independent (ENi) pathway for L1 retrotransposition. Interestingly, some ENi retrotransposition events in DNA protein kinase catalytic subunit-deficient cells are targeted to dysfunctional telomeres. Here we used an in vitro assay to detect L1 reverse transcriptase activity to demonstrate that wild-type or endonuclease-defective L1 ribonucleoprotein particles can use oligonucleotide adapters that mimic telomeric ends as primers to initiate the reverse transcription of L1 mRNA. Importantly, these ribonucleoprotein particles also contain a nuclease activity that can process the oligonucleotide adapters before the initiation of reverse transcription. Finally, we demonstrate that ORF1p is not strictly required for ENi retrotransposition at dysfunctional telomeres. Thus, these data further highlight similarities between the mechanism of ENi L1 retrotransposition and telomerase.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 19
    Publication Date: 2011-12-21
    Description: “Two independent groups of investigators have found evidence of an enzyme… which synthesizes DNA from an RNA template. This discovery, if upheld, will have important implications… information transfer from DNA to RNA can be inverted.” 1970, preamble to refs. 1 and 2.These words accompanied two articles describing the discovery of RNA-dependent DNA polymerase, now known as reverse transcriptase (RT), in the virions of RNA tumor viruses. RT activity was recognized independently by David Baltimore (1) and Howard Temin and Satoshi Mizutani (2). In five printed pages these authors collectively challenged the unidirectionality of macromolecular synthesis, from DNA to RNA to...
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 20
    Publication Date: 2011-12-21
    Description: Reverse transcriptases have shaped genomes in many ways. A remarkable example of this shaping is found on telomeres of the genus Drosophila, where retrotransposons have a vital role in chromosome structure. Drosophila lacks telomerase; instead, three telomere-specific retrotransposons maintain chromosome ends. Repeated transpositions to chromosome ends produce long head to tail arrays of these elements. In both form and function, these arrays are analogous to the arrays of repeats added by telomerase to chromosomes in other organisms. Distantly related Drosophila exhibit this variant mechanism of telomere maintenance, which was established before the separation of extant Drosophila species. Nevertheless, the telomere-specific elements still have the hallmarks that characterize non-long terminal repeat (non-LTR) retrotransposons; they have also acquired characteristics associated with their roles at telomeres. These telomeric retrotransposons have shaped the Drosophila genome, but they have also been shaped by the genome. Here, we discuss ways in which these three telomere-specific retrotransposons have been modified for their roles in Drosophila chromosomes.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 21
    Publication Date: 2011-12-21
    Description: Telomerase is a specialized reverse transcriptase containing an intrinsic telomerase RNA (TR) which provides the template for telomeric DNA synthesis. Distinct from conventional reverse transcriptases, telomerase has evolved a unique TR-binding domain (TRBD) in the catalytic telomerase reverse transcriptase (TERT) protein, integral for ribonucleoprotein assembly. Two structural elements in the vertebrate TR, the pseudoknot and CR4/5, bind TERT independently and are essential for telomerase enzymatic activity. However, the details of the TR–TERT interaction have remained elusive. In this study, we employed a photoaffinity cross-linking approach to map the CR4/5-TRBD RNA–protein binding interface by identifying RNA and protein residues in close proximity. Photoreactive 5-iodouridines were incorporated into the medaka CR4/5 RNA fragment and UV cross-linked to the medaka TRBD protein fragment. The cross-linking RNA residues were identified by alkaline partial hydrolysis and cross-linked protein residues were identified by mass spectrometry. Three CR4/5 RNA residues (U182, U187, and U205) were found cross-linking to TRBD amino acids Tyr503, Phe355, and Trp477, respectively. This CR4/5 binding pocket is distinct and separate from the previously proposed T pocket in the Tetrahymena TRBD. Based on homologous structural models, our cross-linking data position the essential loop L6.1 adjacent to the TERT C-terminal extension domain. We thus propose that stem-loop 6.1 facilitates proper TERT folding by interacting with both TRBD and C-terminal extension. Revealing the telomerase CR4/5-TRBD binding interface with single-residue resolution provides important insights into telomerase ribonucleoprotein architecture and the function of the essential CR4/5 domain.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 22
    Publication Date: 2011-12-21
    Description: Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients. Here, we demonstrate an increase in the retrotransposition efficiency of engineered human L1s in cells that lack or contain severely reduced levels of ataxia telangiectasia mutated, a serine/threonine kinase involved in DNA damage signaling and neurodegenerative disease. We demonstrate that the increase in L1 retrotransposition in ataxia telangiectasia mutated-deficient cells most likely occurs by conventional target-site primed reverse transcription and generate either longer, or perhaps more, L1 retrotransposition events per cell. Finally, we provide evidence suggesting an increase in human-specific L1 DNA copy number in postmortem brain tissue derived from ataxia telangiectasia patients compared with healthy controls. Together, these data suggest that cellular proteins involved in the DNA damage response may modulate L1 retrotransposition.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 23
    Publication Date: 2011-12-21
    Description: Reverse transcriptases (RTs) polymerize DNA on RNA templates. They fall into several structurally related but distinct classes and form an assemblage of RT-like enzymes that, in addition to RTs, also includes certain viral RNA-dependent RNA polymerases (RdRP) synthesizing RNA on RNA templates. It is generally believed that most RT-like enzymes originate from retrotransposons or viruses and have no specific function in the host cell, with telomerases being the only notable exception. Here we report on the discovery and properties of a unique class of RT-related cellular genes collectively named rvt. We present evidence that rvts are not components of retrotransposons or viruses, but single-copy genes with a characteristic domain structure that may contain introns in evolutionarily conserved positions, occur in syntenic regions, and evolve under purifying selection. These genes can be found in all major taxonomic groups including protists, fungi, animals, plants, and even bacteria, although they exhibit patchy phylogenetic distribution in each kingdom. We also show that the RVT protein purified from one of its natural hosts, Neurospora crassa, exists in a multimeric form and has the ability to polymerize NTPs as well as dNTPs in vitro, with a strong preference for NTPs, using Mn2+ as a cofactor. The existence of a previously unknown class of single-copy RT-related genes calls for reevaluation of the current views on evolution and functional roles of RNA-dependent polymerases in living cells.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 24
    Publication Date: 2011-12-21
    Description: Telomerase copies its internal RNA template to synthesize telomeric DNA repeats. Unlike other polymerases, telomerase can retain its single-stranded product through multiple rounds of template dissociation and repositioning to accomplish repeat addition processivity (RAP). Tetrahymena telomerase holoenzyme RAP depends on a subunit, Teb1, with autonomous DNA-binding activity. Sequence homology and domain modeling suggest that Teb1 is a paralog of RPA70C, the largest subunit of the single-stranded DNA-binding factor replication protein (RPA), but unlike RPA, Teb1 binds DNA with high specificity for telomeric repeats. To understand the structural basis and significance of telomeric-repeat DNA recognition by Teb1, we solved crystal structures of three proposed Teb1 DNA-binding domains and defined amino acids of each domain that contribute to DNA interaction. Our studies indicate that two central Teb1 DNA-binding oligonucleotide/oligosaccharide-binding-fold domains, Teb1A and Teb1B, achieve high affinity and selectivity of telomeric-repeat recognition by principles similar to the telomere end-capping protein POT1 (protection of telomeres 1). An additional C-terminal Teb1 oligonucleotide/oligosaccharide-binding-fold domain, Teb1C, has features shared with the RPA70 C-terminal domain including a putative direct DNA-binding surface that is critical for high-RAP activity of reconstituted holoenzyme. The Teb1C zinc ribbon motif does not contribute to DNA binding but is nonetheless required for high-RAP activity, perhaps contributing to Teb1 physical association with the remainder of the holoenzyme. Our results suggest the biological model that high-affinity DNA binding by Teb1AB recruits holoenzyme to telomeres and subsequent Teb1C–DNA association traps product in a sliding-clamp-like manner that does not require high-affinity DNA binding for high stability of enzyme-product association.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 25
    Publication Date: 2011-12-21
    Description: The yeast telomerase regulatory protein Est3 is required for telomere maintenance in vivo, and shares intriguing structural and functional similarities with the mammalian telomeric protein TPP1. Here we report our physical and functional characterizations of Est3 homologues from Candida parapsilosis and Lodderomyces elongisporus, which bear unique N- and C-terminal tails in addition to a conserved central OB fold. We show that these Est3 homologues form stable complexes with the TEN domain of telomerase reverse transcriptase. Efficient complex formation requires both the N- and C-terminal tails, as well as conserved OB fold residues of Est3. Other Est3 homologues devoid of the tails failed to interact strongly with the cognate TEN domains. Remarkably, the C. parapsilosis Est3 alone exhibits no appreciable DNA-binding activity, but can be crosslinked to telomeric DNA in the presence of the TEN domain. A conserved basic residue on the putative DNA-binding surface of CpEst3 is required for efficient crosslinking. Mutating the equivalent residue in Candida albicans Est3 caused telomere attrition. We propose that interaction with the TEN domain unmasks a functionally important nucleic acid-binding activity in Est3. Our findings provide insights on the mechanisms and evolution of a widely conserved and functionally critical telomeric/telomerase component.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 26
    Publication Date: 2011-12-21
    Description: In Saccharomyces cerevisiae, a Cdc13–Est1 interaction is proposed to mediate recruitment of telomerase to DNA ends. Here we provide unique in vitro evidence for this model by demonstrating a direct interaction between purified Cdc13 and Est1. The Cdc13–Est1 interaction is specific and requires the in vivo defined Cdc13 recruitment domain. Moreover, in the absence of this interaction, Est1 is excluded from telomeric single-stranded (ss)DNA. The apparent association constand (Kd) between Est1 and a Cdc13-telomeric ssDNA complex was ∼250 nM. In G2 phase cells, where telomerase is active, Cdc13 and Est1 were sufficiently abundant (∼420 and ∼110 copies per cell, respectively) to support complex formation. Interaction between Cdc13 and Est1 was unchanged by three telomerase-deficient mutations, Cdc13E252K (cdc13-2), Est1K444E (est1-60), and Cdc13S249,255D, indicating that their telomerase null phenotypes are not due to loss of the Cdc13–Est1 interaction. These data recapitulate in vitro the first step in telomerase recruitment to telomeric ssDNA and suggest that this step is necessary to recruit telomerase to DNA ends.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
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  • 27
    Publication Date: 2011-12-21
    Description: Genetic damage through mutations and genome rearrangements has been hypothesized to contribute to aging. The specific mechanisms responsible for age-induced increases in mutation and chromosome rearrangement frequencies and a potential causative role for DNA damage in aging are under active investigation. Retrotransposons are mobile genetic elements that cause insertion mutations and contribute to genome rearrangements through nonallelic recombination events in humans and other organisms. We have investigated the role of endogenous Ty1 retrotransposons in aging-associated increases in genome instability using the Saccharomyces cerevisiae chronological aging model. We show that age-induced increases in loss of heterozygosity and chromosome loss events are consistently diminished by mutations or treatments that reduce Ty1 retrotransposition. Ty1 mobility is elevated in very old yeast populations, and new retromobility events are often associated with chromosome rearrangements. These results reveal a correlation between retrotransposition and genome instability during yeast aging. Retrotransposition may contribute to genetic damage during aging in diverse organisms and provides a useful tool for studying whether genetic damage is a causative factor for aging.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 28
    Publication Date: 2011-12-21
    Description: Telomerase ribonucleoprotein (RNP) employs an RNA subunit to template the addition of telomeric repeats onto chromosome ends. Previous studies have suggested that a region of the RNA downstream of the template may be important for telomerase activity and that the region could fold into a pseudoknot. Whether the pseudoknot motif is formed in the active telomerase RNP and what its functional role is have not yet been conclusively established. Using single-molecule FRET, we show that the isolated pseudoknot sequence stably folds into a pseudoknot. However, in the context of the full-length telomerase RNA, interference by other parts of the RNA prevents the formation of the pseudoknot. The protein subunits of the telomerase holoenzyme counteract RNA-induced misfolding and allow a significant fraction of the RNPs to form the pseudoknot structure. Only those RNP complexes containing a properly folded pseudoknot are catalytically active. These results not only demonstrate the functional importance of the pseudoknot but also reveal the critical role played by telomerase proteins in pseudoknot folding.
    Keywords: Telomerase and Retrotransposons: Reverse Transcriptases That Shaped Genomes Sackler Special Feature
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Location Call Number Expected Availability
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