Nonbinary people: Perceived social support in personal relationships and (virtual) communities.

Background: Nonbinary individuals grapple with societal and individual pressures from a pervasive lack of comprehension, acknowledgment, and affirmative social representation. This dearth of a societal conversation recognizing the validity of nonbinary identities leads to instances of discrimination. Social support is recognized as a buffer to these experiences and is positively related to better physical and psychological health.

Pediatric population with cystic fibrosis in the centre of Portugal: candidates for new therapies.

Objectives: Cystic fibrosis (CF) is a severe autosomal recessive disease that results from mutations in a gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, a chloride channel. This study aims to characterize the clinical and genetic features of a cohort of pediatric people with CF (PwCF) in the center of Portugal and to determine which ones are candidates for the new drugs modulating the CFTR channel.

Methods: A review of the demographic, genetic and clinical characteristics of PwCF undergoing follow-up at a CF reference center was carried out.

Saccharomyces cerevisiae as a Model to Study Replicative Senescence Triggered by Telomere Shortening.

In many somatic human tissues, telomeres shorten progressively because of the DNA-end replication problem. Consequently, cells cease to proliferate and are maintained in a metabolically viable state called replicative senescence. These cells are characterized by an activation of DNA damage checkpoints stemming from eroded telomeres, which are bypassed in many cancer cells.

CST meets shelterin to keep telomeres in check.

Telomere protection in budding yeast requires the heterotrimer named CST (for Cdc13-Stn1-Ten1). Recent data show that CST components are conserved and required for telomere stability in a wide range of eukaryotes, even those utilizing the shelterin complex to protect their telomeres. A common function of these proteins might be to stimulate priming at the C-strand gap that remains after telomerase elongation, replication termination, and terminal processing.

Telomerase and chromosome end protection in vivo: the TPP1 connection.

In an article published in this issue of Developmental Cell, Maria Blasco's group shows that the telomere end-binding protein TPP1 is involved in both end protection and telomerase regulation in vivo. Importantly, they highlight the relevance of telomerase activity in highly proliferative tissues and in reprogramming of cells to induced pluripotency (iPS).

The DNA damage response at eroded telomeres and tethering to the nuclear pore complex.

The ends of linear eukaryotic chromosomes are protected by telomeres, which serve to ensure proper chromosome replication and to prevent spurious recombination at chromosome ends. In this study, we show by single cell analysis that in the absence of telomerase, a single short telomere is sufficient to induce the recruitment of checkpoint and recombination proteins. Notably, a DNA damage response at eroded telomeres starts many generations before senescence and is characterized by the recruitment of Cdc13 (cell division cycle 13), replication protein A, DNA damage checkpoint proteins and the DNA repair protein Rad52 into a single focus.

A two-step model for senescence triggered by a single critically short telomere.

Telomeres protect chromosome ends from fusion and degradation. In the absence of a specific telomere elongation mechanism, their DNA shortens progressively with every round of replication, leading to replicative senescence. Here, we show that telomerase-deficient cells bearing a single, very short telomere senesce earlier, demonstrating that the length of the shortest telomere is a major determinant of the onset of senescence.

When CDK1 rides the telomere cycle.

Reconstitution of telomeric DNA at each cell division implies the coordination of DNA semiconservative replication with several processing events still poorly understood. Two reports published recently in Molecular Cell show that a cell-cycle cyclin-dependent kinase, Cdk1p, is required to create the cell-cycle-regulated overhang ().

Telomere length homeostasis is achieved via a switch between telomerase- extendible and -nonextendible states.

Telomerase counteracts telomere erosion that stems from incomplete chromosome end replication and nucleolytic processing. A precise understanding of telomere length homeostasis has been hampered by the lack of assays that delineate the nonuniform telomere extension events of single chromosome molecules. Here, we measure telomere elongation at nucleotide resolution in Saccharomyces cerevisiae.

Telomerase: biochemical considerations for enzyme and substrate.

Telomerase extends chromosome ends by iterative reverse transcription of its RNA template. Following the addition of each telomeric repeat, the RNA template and the telomeric substrate reset their relative position in the active site provided by the telomerase reverse transcriptase (TERT). This step might require the formation of guanine-rich secondary structures in the nascent product.

Intracellular trafficking of yeast telomerase components.

Telomerase uses an internal RNA moiety as template for the synthesis of telomere repeats. In Saccharomyces cerevisiae, the telomerase holoenzyme contains the telomerase reverse transcriptase subunit Est2p, the telomerase RNA moiety TLC1, the telomerase associated proteins Est1p and Est3p, and Sm proteins. Here we assess telomerase assembly by determining the localization of telomerase components.