Telomeres

  • Article
    | Open Access

    Single-stranded DNA during DNA replication and repair in S/G2 needs protection by replication protein A (RPA). Here the authors reveal that RPA also shields inherited single-stranded DNA in G1, representing replication remnants from the previous cell cycle, to allow for post-mitotic DNA synthesis.

    • Aleksandra Lezaja
    • , Andreas Panagopoulos
    •  & Matthias Altmeyer
  • Article
    | Open Access

    TERRA RNA has previously been linked to Alternative lengthening of telomeres (ALT). Here the authors developed a tool to rapidly inhibit TERRA transcription from different chromosome ends in an ALT cell line to show that TERRA transcription actively promotes break induced replication (BIR) and destabilizes telomere integrity in ALT cells.

    • Bruno Silva
    • , Rajika Arora
    •  & Claus M. Azzalin
  • Article
    | Open Access

    BRCA1-mediated resolution of R-loops has previously been described. Here the authors reveal a functional association of BRCA1 with TERRA RNA at telomeres, which develops in an R-loop-, and a cell cycle-dependent manner.

    • Jekaterina Vohhodina
    • , Liana J. Goehring
    •  & David M. Livingston
  • Article
    | Open Access

    Different proteins localised at telomeres ensure chromosome end stability to prevent double strand-end break recognition. Here the authors provide new insight into how in S. cerevisiae the interaction between Rif2 and Rad50 inhibits MRX functions at telomeres.

    • Florian Roisné-Hamelin
    • , Sabrina Pobiega
    •  & Stéphane Marcand
  • Article
    | Open Access

    Telomeres, tandem repeats at the ends of linear chromosomes, have evolved to deal with the end replication and end protection. Using a proteomics approach, the authors identify TEBP-1 and TEBP-2, two double-stranded binding proteins which together are required for fertility. Despite being paralogs, they have distinct individual effects on telomere dynamics; TEBP-1 and TEBP-2 are part of a telomeric complex also containing POT-1.

    • Sabrina Dietz
    • , Miguel Vasconcelos Almeida
    •  & Falk Butter
  • Article
    | Open Access

    Alternative Lengthening of Telomeres (ALT) is a telomere maintenance pathway utilised in 15% of cancers that have been associated with mutations in ATRX. Here the authors reveal a functional role of histone demethylases KDM4B in regulating ALT activation.

    • M. Udugama
    • , L. Hii
    •  & L. H. Wong
  • Article
    | Open Access

    Telomere crisis has been shown to induce chromothripsis and breakage fusion bridge (BFB) cycles in vitro. Here, the authors show that telomere crisis generates a much broader spectrum of structural variations, implying that cancers without chromothripsis and BFB cycles could have emerged from telomere crisis.

    • Sally M. Dewhurst
    • , Xiaotong Yao
    •  & Marcin Imieliński
  • Article
    | Open Access

    Telomeres can be maintained by a telomerase-independent mechanism called an alternative lengthening of telomeres (ALT). Here the authors use mouse Terc (telomerase RNA) knockout embryonic cells and provide longitudinal analysis of ALT telomeres maintained with non-telomeric sequences.

    • Chuna Kim
    • , Sanghyun Sung
    •  & Junho Lee
  • Article
    | Open Access

    Pyruvate kinase phosphorylates histone H3T11 (H3pT11) and represses gene expression by forming a large complex SESAME (Serine-responsive SAM-containing Metabolic Enzyme). Here the authors show that SESAME-catalyzed H3pT11 regulates telomere silencing by promoting Sir2 binding at telomeres and preventing autophagy-mediated Sir2 degradation.

    • Shihao Zhang
    • , Xilan Yu
    •  & Shanshan Li
  • Article
    | Open Access

    ~15% of cancers induce alternative lengthening of telomeres (ALT) to activate telomere maintenance. Here, the authors reveal that infection with Kaposi’s sarcoma herpesvirus (KSHV) induces acquisition of ALT-like features in previously non-ALT cell lines.

    • Timothy P. Lippert
    • , Paulina Marzec
    •  & Simon J. Boulton
  • Article
    | Open Access

    Telomerase enzymes add telomeric repeats to the end of linear chromosomes. Here the authors reveal mechanisms by which oxidized dNTPs and therapeutic dNTPs inhibit telomerase-mediated telomere elongation.

    • Samantha L. Sanford
    • , Griffin A. Welfer
    •  & Patricia L. Opresko
  • Article
    | Open Access

    Telomere function is regulated by the telomere repeat binding proteins TRF1 and TRF2. Here the authors show that decreased levels of TRF1 proteins at shortened telomeres in aged human cells results in persistent telomere cohesion, protecting from premature senescence.

    • Kameron Azarm
    • , Amit Bhardwaj
    •  & Susan Smith
  • Article
    | Open Access

    Pop1 and 6 are subunits of RNase P and RNase MRP, which process ribosomal and tRNAs. The authors show that when Pop1 and 6 are impaired, the telomerase subunit Est1 binds telomerase RNA at normal levels, but the binding is unstable. As a result, nuclear import of the telomerase holoenzyme is inhibited.

    • P. Daniela Garcia
    • , Robert W. Leach
    •  & Virginia A. Zakian
  • Article
    | Open Access

    Major effect loci controlling natural, heritable variation in telomere length are not known. Here, the authors use QTL mapping and transgenic manipulations in Arabidopsis to implicate the rRNA-processing genes NOP2A and RPL5 in telomere length set point regulation in this model species.

    • Liliia R. Abdulkina
    • , Callie Kobayashi
    •  & Eugene V. Shakirov
  • Article
    | Open Access

    Hutchinson–Gilford progeria syndrome causes premature aging. Here the authors show that activation of the DNA damage response at dysfunctional telomeres and transcription of telomeric non-coding RNAs contributes to the pathogenesis, which can be ameliorated by treatment with sequence-specific telomeric antisense oligonucleotides.

    • Julio Aguado
    • , Agustin Sola-Carvajal
    •  & Fabrizio d’Adda di Fagagna
  • Article
    | Open Access

    Conversion of dermal fibroblasts into Cancer Associated Fibroblasts (CAFs) can play an important role in keratinocyte tumour development. Here the authors reveal that CSL plays a role in maintenance of telomeres and genomic integrity in both dermal fibroblasts and CAFs.

    • Giulia Bottoni
    • , Atul Katarkar
    •  & G. Paolo Dotto
  • Article
    | Open Access

    Shortening of leukocyte telomere length (LTL) is associated with age and increased risk for various chronic diseases. Here, the authors report genome-wide association studies for LTL in Singaporean Chinese populations and find that longer LTL associates with less severe outcomes of respiratory disease phenotypes.

    • Rajkumar Dorajoo
    • , Xuling Chang
    •  & Chew-Kiat Heng
  • Article
    | Open Access

    LncRNA TERRA forms RNA-DNA hybrids at telomere sites leading to telomere instability. Here the authors identify the RNA interacting factors NONO and SFPQ as proteins that interact with TERRA and telomere chromatin and reveal putative roles for these factors in telomere integry maintenance by interfering with RNA:DNA hybrid formation.

    • Eleonora Petti
    • , Valentina Buemi
    •  & Stefan Schoeftner
  • Article
    | Open Access

    Chromatin dynamics is thought to play an important role in the maintenance of telomeres, yet how has remained poorly understood. Here the authors locally enrich heterochromatin protein 1α (HP1α) at human telomeres to provide insights into the crosstalk between epigenetic regulations and structural dynamics at the telomeres.

    • Tracy T. Chow
    • , Xiaoyu Shi
    •  & Elizabeth H. Blackburn
  • Article
    | Open Access

    The human CST complex (CTC1-STN1-TEN1) is essential for telomere homeostasis. Here the authors dissect the roles of individual CST subunits in telomere length maintenance through regulation of telomerase-mediated G-strand synthesis and DNA polymerase-mediated C-strand synthesis in colon cancer cells.

    • Xuyang Feng
    • , Shih-Jui Hsu
    •  & Carolyn M. Price
  • Article
    | Open Access

    Mutations in the RNA component TERC can cause telomerase dysfunction but the underlying mechanisms are largely unknown. Here, the authors show that RNA-binding protein HuR regulates telomerase function by enhancing the methylation of TERC, which is impaired by several disease-relevant TERC mutations.

    • Hao Tang
    • , Hu Wang
    •  & Wengong Wang
  • Article
    | Open Access

    Glioblastoma can be classified based on IDH and TERT promoter mutations, but ~20% of glioblastoma do not have these mutations (TERTpWT-IDHWT glioblastoma). Here, the authors present a genetic landscape of TERTpWT-IDHWT glioblastoma, identifying a telomerase-positive subgroup driven by TERT-structural rearrangements and an ALT-positive subgroup with mutations in ATRX or SMARCAL1.

    • Bill H. Diplas
    • , Xujun He
    •  & Hai Yan
  • Article
    | Open Access

    The core of the telomerase holoenzyme is composed of the reverse transcriptase and the non-coding RNA template. Here the authors identify Pof8 as a new constitutive component of fission yeast telomerase, loss of which causes telomerase assembly defects and critically short telomeres.

    • Diego J. Páez-Moscoso
    • , Lili Pan
    •  & Peter Baumann
  • Article
    | Open Access

    The telomerase holoenzyme is minimally composed of the reverse transcriptase and the RNA template. Here the authors identify Lar7 as a member of the full complex that helps to stabilise it and protect telomerase RNA from degradation.

    • Laura C. Collopy
    • , Tracy L. Ware
    •  & Kazunori Tomita
  • Article
    | Open Access

    TERRA RNA is involved in maintaining stability during telomere repeat replication. Here the authors, by using CRISPR/Cas9, mutate CTCF-binding sites at start site of TERRA transcripts and find that subtelomeric CTCF facilitates telomeric DNA replication by promoting TERRA transcription.

    • Kate Beishline
    • , Olga Vladimirova
    •  & Paul M. Lieberman
  • Article
    | Open Access

    How both telomere stability is regulated and dysfunctional telomeres processed in quiescent cells is poorly understood. Here, the authors provide evidence that eroded telomeres in quiescent fission yeast are rearranged by homologous recombination through duplications of subtelomeric sequences.

    • Laetitia Maestroni
    • , Julien Audry
    •  & Stéphane Coulon
  • Article
    | Open Access

    Regulation of telomeres and the insulin/PI3K pathway both have roles in aging and cancer development but have not been functionally linked. Here the authors demonstrate that PI3K, via downstream targets, regulates TRF1 via phosphorylation.

    • Marinela Méndez-Pertuz
    • , Paula Martínez
    •  & Maria A. Blasco
  • Article
    | Open Access

    The human shelterin complex protects telomere ends from being recognized as damaged DNA sites and regulates telomere length in conjunction with telomerase. Here the authors establish the stoichiometries of human shelterin complexes of various compositions and show shelterin provides dual pathways to stimulate telomerase processivity.

    • Ci Ji Lim
    • , Arthur J. Zaug
    •  & Thomas R. Cech
  • Article
    | Open Access

    POT1 and TTP1 are part of the shelterin complex that caps and stabilizes the ends of telomeres. Here the authors present a structural analysis of the human POT1-TTP1 complex, shedding light on how it assembles and how cancer-associated mutations impact its assembly and function.

    • Cory Rice
    • , Prashanth Krishna Shastrula
    •  & Emmanuel Skordalakes
  • Article
    | Open Access

    The DNA damage response (DDR) involves site-specific small non-coding RNAs. Here the authors show that telomere dysfunction induces transcription of telomeric DNA damage response RNAs that are necessary for DDR activation, which can be specifically muted by antisense inhibitory oligonucleotides.

    • Francesca Rossiello
    • , Julio Aguado
    •  & Fabrizio d’Adda di Fagagna
  • Article
    | Open Access

    The telomeric long-non coding RNA, TERRA, has been proposed in the past to modulate different telomeric functions based on in vitrostudies. Here the authors show, using a genetic deletion approach, that TERRA is transcribed from the 20q subtelomere and that it is essential for telomere maintenance.

    • Juan José Montero
    • , Isabel López de Silanes
    •  & Maria A. Blasco
  • Article
    | Open Access

    Telomere shortening has been linked to some aspects of organismal ageing. Here the authors create chimaeric mice that contain a mix of cells with normal or unnaturally long telomeres, and show chimaeric mice are protected from some forms of ageing-associated cellular damage and have accelerated wound-healing.

    • Elisa Varela
    • , Miguel A. Muñoz-Lorente
    •  & Maria A. Blasco
  • Article
    | Open Access

    A chromosome is composed of structurally and functionally distinct domains. Here, Tashiro et al. report that the conserved centromeric protein Sgo2 localizes at the subtelomeres preferentially during G2phase and is essential for the formation of a highly condensed subtelomeric chromatin body “knob”.

    • Sanki Tashiro
    • , Tetsuya Handa
    •  & Junko Kanoh
  • Article
    | Open Access

    Drosophila telomeres are elongated by transposition of specialized retroelements rather than telomerase activity. Here, the authors show that Separase is enriched at Drosophila telomeres and loss of Sse, the gene encoding Separase, leads to telomere defects, suggesting a role for Separase in telomere protection.

    • Francesca Cipressa
    • , Patrizia Morciano
    •  & Giovanni Cenci