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Telomere maintenance is crucial for preventing the linear eukaryotic chromosome ends from being mistaken for DNA double-strand breaks, thereby avoiding chromosome fusions and the loss of genetic material. Unlike most eukaryotes that use telomerase for telomere maintenance, relies on retrotransposable elements-specifically , , and (collectively referred to as HTT)-which are regulated and precisely targeted to chromosome ends. telomere protection is mediated by a set of fast-evolving proteins, termed terminin, which bind to chromosome termini without sequence specificity, balancing DNA damage response factors to avoid erroneous repair mechanisms. This unique telomere capping mechanism highlights an alternative evolutionary strategy to compensate for telomerase loss. The modulation of recombination and transcription at telomeres offers insights into the diverse mechanisms of telomere maintenance. Recent studies at the population level have begun to reveal the architecture of telomere arrays, the diversity among the HTT subfamilies, and their relative frequencies, aiming to understand whether and how these elements have evolved to reach an equilibrium with the host and to resolve genetic conflicts. Further studies may shed light on the complex relationships between telomere transcription, recombination, and maintenance, underscoring the adaptive plasticity of telomeric complexes across eukaryotes.
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http://dx.doi.org/10.1101/cshperspect.a041708 | DOI Listing |
Front Immunol
September 2025
Department of Medicine, Division of Hematology, Bioclinicum and Center for Molecular Medicine, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden.
Background: Metabolic reprogramming is an important hallmark of cervical cancer (CC), and extensive studies have provided important information for translational and clinical oncology. Here we sought to determine metabolic association with molecular aberrations, telomere maintenance and outcomes in CC.
Methods: RNA sequencing data from TCGA cohort of CC was analyzed for their metabolic gene expression profile and consensus clustering was then performed to classify tumors into different groups/subtypes.
Biomed Pharmacother
September 2025
Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Polyploidy, a conserved mechanism involved in normal development and tissue homeostasis, plays a paradoxical role in cancer by facilitating both tumor progression and therapeutic vulnerability. Although polyploidization may confer survival advantages to cancer cells, its controlled induction could represent an effective anticancer strategy. Aurora B kinase, a critical regulator of mitosis, plays a pivotal role in ensuring chromosomal integrity and preventing polyploidy.
View Article and Find Full Text PDFNucleic Acids Res
September 2025
Department of Genetics, Comenius University Bratislava, Faculty of Natural Sciences, Ilkovičova 6, 842 15 Bratislava, Slovakia.
Poly (ADP-ribose) polymerases (PARPs) are enzymes catalyzing the post-translational addition of chains of ADP-ribose moieties to proteins. In most eukaryotic cells, their primary protein targets are involved in DNA recombination, repair, and chromosome maintenance. Even though this group of enzymes is quite common in both eukaryotes and prokaryotes, no PARP homologs have been described so far in ascomycetous yeasts, leaving their potential roles in this group of organisms unexplored.
View Article and Find Full Text PDFAging Cell
September 2025
Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
The CST (CTC1-STN1-TEN1) complex, a single-stranded DNA (ssDNA) binding complex, is essential for telomere maintenance and genome stability. Depletion of either CTC1 or STN1 results in cellular senescence, while mutations in these components are associated with severe hereditary disorders. In this study, we demonstrate that the direct STN1-CTC1 interaction stabilizes CTC1 by preventing its degradation via TRIM32 mediated ubiquitination.
View Article and Find Full Text PDFBiochemistry
September 2025
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, United States.
SAMHD1 (SAM domain and HD domain-containing protein 1) is a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) with functions in viral restriction, R-loop resolution, DNA repair, telomere maintenance, ssRNA homeostasis, and regulation of self-nucleic acids. As a dNTPase, SAMHD1 functions as an allosterically activated tetramer, where binding of GTP to the A1 activator site of each monomer initiates dNTP-dependent tetramerization. cEM structures reveal that the nucleic-acid-related functions of SAMHD1 involve binding of guanine residues to the A1 site, leading to oligomeric forms that appear as beads-on-a-string on single-stranded RNA and DNA.
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