Biology of telomeres: lessons from budding yeast

Kupiec, Martin

doi:10.1111/1574-6976.12054

Cited by 90 publications

(88 citation statements)

References 353 publications

(592 reference statements)

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“…Telomeres are nucleoprotein structures, at the ends of eukaryotic chromosomes, involved in maintaining genomic fidelity. Telomere shortening has been associated with aging and aging-related diseases [44]. Contrary to our expectations, we observed no association of PM 2.5 and BC with relative TL.…”

Section: Discussioncontrasting

confidence: 99%

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

et al. 2016

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BackgroundAmbient particles have been shown to exacerbate measures of biological aging; yet, no studies have examined their relationships with DNA methylation age (DNAm-age), an epigenome-wide DNA methylation based predictor of chronological age.ObjectiveWe examined the relationship of DNAm-age with fine particulate matter (PM2.5), a measure of total inhalable particle mass, and black carbon (BC), a measure of particles from vehicular traffic.MethodsWe used validated spatiotemporal models to generate 1-year PM2.5 and BC exposure levels at the addresses of 589 older men participating in the VA Normative Aging Study with 1–3 visits between 2000 and 2011 (n = 1032 observations). Blood DNAm-age was calculated using 353 CpG sites from the Illumina HumanMethylation450 BeadChip. We estimated associations of PM2.5 and BC with DNAm-age using linear mixed effects models adjusted for age, lifestyle/environmental factors, and aging-related diseases.ResultsAfter adjusting for covariates, a 1-µg/m3 increase in PM2.5 (95% CI: 0.30, 0.75, P<0.0001) was significantly associated with a 0.52-year increase in DNAm-age. Adjusted BC models showed similar patterns of association (β = 3.02, 95% CI: 0.48, 5.57, P = 0.02). Only PM2.5 (β = 0.54, 95% CI: 0.24, 0.84, P = 0.0004) remained significantly associated with DNAm-age in two-particle models. Methylation levels from 20 of the 353 CpGs contributing to DNAm-age were significantly associated with PM2.5 levels in our two-particle models. Several of these CpGs mapped to genes implicated in lung pathologies including LZTFL1, PDLIM5, and ATPAF1.ConclusionOur results support an association of long-termambient particle levels with DNAm-age and suggest that DNAm-age is a biomarker of particle-related physiological processes.

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Section: Discussioncontrasting

confidence: 99%

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

et al. 2016

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“…lactis , and C . neoformans , some of which perform symetrical divisions by fission, similar to what is observed in Chlamydomonas (reviewed in [23,24,107]). Their study has greatly benefited from the knowledge of the aging process in the well-studied, asymmetrically dividing, budding yeast Saccharomyces cerevisiae , that has been reported as early as 1959 [17].…”

Section: Discussionmentioning

confidence: 84%

A Millifluidic Study of Cell-to-Cell Heterogeneity in Growth-Rate and Cell-Division Capability in Populations of Isogenic Cells of Chlamydomonas reinhardtii

et al. 2015

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To address possible cell-to-cell heterogeneity in growth dynamics of isogenic cell populations of Chlamydomonas reinhardtii, we developed a millifluidic drop-based device that not only allows the analysis of populations grown from single cells over periods of a week, but is also able to sort and collect drops of interest, containing viable and healthy cells, which can be used for further experimentation. In this study, we used isogenic algal cells that were first synchronized in mixotrophic growth conditions. We show that these synchronized cells, when placed in droplets and kept in mixotrophic growth conditions, exhibit mostly homogeneous growth statistics, but with two distinct subpopulations: a major population with a short doubling-time (fast-growers) and a significant subpopulation of slowly dividing cells (slow-growers). These observations suggest that algal cells from an isogenic population may be present in either of two states, a state of restricted division and a state of active division. When isogenic cells were allowed to propagate for about 1000 generations on solid agar plates, they displayed an increased heterogeneity in their growth dynamics. Although we could still identify the original populations of slow- and fast-growers, drops inoculated with a single progenitor cell now displayed a wider diversity of doubling-times. Moreover, populations dividing with the same growth-rate often reached different cell numbers in stationary phase, suggesting that the progenitor cells differed in the number of cell divisions they could undertake. We discuss possible explanations for these cell-to-cell heterogeneities in growth dynamics, such as mutations, differential aging or stochastic variations in metabolites and macromolecules yielding molecular switches, in the light of single-cell heterogeneities that have been reported among isogenic populations of other eu- and prokaryotes.

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“…To demonstrate proof of concept for the aforementioned rationale, we initially applied the SGA procedure to the yeast lincRNA TLC1 , which has a well-defined cellular role in telomere maintenance [27, 28]. The SGA screen was carried out in duplicate by combining the tlc1Δ strain against an ordered array of approximately 4300 viable protein-coding gene deletion strains.…”

Section: Resultsmentioning

confidence: 99%

“…TLC1 has a functional orthologue in human cells, known as TERC [26], but these two RNAs vary in size and nucleotide sequence. TLC1 is transcribed on chromosome II and then interacts physically with proteins Est1, Est2 and Est3 to form the telomerase complex, whose role is to solve the end replication problem by synthesising telomeric DNA repeats and preventing telomere shortening during each cell division [27, 28]. TLC1 is recruited to telomeres through a chain of physical interactions coordinated by the heterodimeric Ku complex (yKu70/yKu80) [29–31].…”

Section: Introductionmentioning

confidence: 99%

Functional characterisation of long intergenic non-coding RNAs through genetic interaction profiling in Saccharomyces cerevisiae

et al. 2016

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BackgroundTranscriptome studies have revealed that many eukaryotic genomes are pervasively transcribed producing numerous long non-coding RNAs (lncRNAs). However, only a few lncRNAs have been ascribed a cellular role thus far, with most regulating the expression of adjacent genes. Even less lncRNAs have been annotated as essential hence implying that the majority may be functionally redundant. Therefore, the function of lncRNAs could be illuminated through systematic analysis of their synthetic genetic interactions (GIs).ResultsHere, we employ synthetic genetic array (SGA) in Saccharomyces cerevisiae to identify GIs between long intergenic non-coding RNAs (lincRNAs) and protein-coding genes. We first validate this approach by demonstrating that the telomerase RNA TLC1 displays a GI network that corresponds to its well-described function in telomere length maintenance. We subsequently performed SGA screens on a set of uncharacterised lincRNAs and uncover their connection to diverse cellular processes. One of these lincRNAs, SUT457, exhibits a GI profile associating it to telomere organisation and we consistently demonstrate that SUT457 is required for telomeric overhang homeostasis through an Exo1-dependent pathway. Furthermore, the GI profile of SUT457 is distinct from that of its neighbouring genes suggesting a function independent to its genomic location. Accordingly, we show that ectopic expression of this lincRNA suppresses telomeric overhang accumulation in sut457Δ cells assigning a trans-acting role for SUT457 in telomere biology.ConclusionsOverall, our work proposes that systematic application of this genetic approach could determine the functional significance of individual lncRNAs in yeast and other complex organisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0325-7) contains supplementary material, which is available to authorized users.

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Biology of telomeres: lessons from budding yeast

Cited by 90 publications

References 353 publications

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

A Millifluidic Study of Cell-to-Cell Heterogeneity in Growth-Rate and Cell-Division Capability in Populations of Isogenic Cells of Chlamydomonas reinhardtii

Functional characterisation of long intergenic non-coding RNAs through genetic interaction profiling in Saccharomyces cerevisiae

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