Telomeres articles within Nature

Featured

  • Article |

    Cryogenic electron microscopy analyses reveal a new, compact structure of telomeric chromatin, providing mechanistic insight into telomere maintenance and function.

    • Aghil Soman
    • , Sook Yi Wong
    •  & Lars Nordenskiöld

  • Article |

    A high-resolution structure of human telomerase bound to telomeric DNA reveals details of telomerase assembly and its active site, and sheds light on how mutations alter telomerase function.

    • George E. Ghanim
    • , Adam J. Fountain
    •  & Thi Hoang Duong Nguyen

  • Article |

    Experiments in mouse pluripotent embryonic and epiblast stem cells show that TRF2 is dispensable for telomere protection specifically specifically in the pluripotent cells that form during early embryonic development, when cells form T-loops independently of this protein.

    • Phil Ruis
    • , David Van Ly
    •  & Simon J. Boulton

  • Article |

    Depletion of TRF2—an essential mediator of telomere protection in most mammalian cells—in mouse embryonic stem cells activates a compensatory transcriptional program that renders TRF2 dispensable for their survival and proliferation.

    • Marta Markiewicz-Potoczny
    • , Anastasia Lobanova
    •  & Eros Lazzerini Denchi

  • Article |

    Telomeric-repeat-containing RNA is recruited to telomeres by a mechanism that involves the DNA recombinase RAD51 and the formation of DNA–RNA hybrids, or R-loops—a process similar to that involved in homology-directed DNA repair.

    • Marianna Feretzaki
    • , Michaela Pospisilova
    •  & Joachim Lingner

  • Article |

    A phospho-switch is identified in the shelterin subunit TRF2 that regulates transient recruitment of the RTEL1 helicase to, and release from, telomeres, and provides a narrow window during which RTEL1 can unwind t-loops to facilitate telomere replication.

    • Grzegorz Sarek
    • , Panagiotis Kotsantis
    •  & Simon J. Boulton

  • Article |

    Successive fusion of yeast chromosomes is used to produce a single-chromosome strain that is viable, albeit with slightly reduced fitness.

    • Yangyang Shao
    • , Ning Lu
    •  & Zhongjun Qin

  • Letter |

    Next-generation sequencing technology is used to show that the error-prone polymerase θ (Polθ) is needed to promote alternative non-homologous end joining at telomeres, and during chromosomal translocations, while counteracting homologous recombination; inhibition of Polθ represents a potential therapeutic strategy for tumours that have mutations in homology-directed repair genes.

    • Pedro A. Mateos-Gomez
    • , Fade Gong
    •  & Agnel Sfeir

  • Article |

    In vitro and in vivo, the yeast Pif1 helicase is able to unwind four-stranded G-quadruplex (G4) DNA efficiently and suppress the genomic instability that occurs at such structures; these G4 maintenance activities are conserved among evolutionarily diverse Pif1 family helicases, including human PIF1, demonstrating the importance of this activity throughout evolution.

    • Katrin Paeschke
    • , Matthew L. Bochman
    •  & Virginia A. Zakian

  • Letter |

    The telomere-biding protein TRF2 is shown to protect telomeres from activating the DNA-damage response through two mechanisms: preventing the activation ATM kinase through its dimerization domain, in addition to independently suppressing signalling events occurring downstream of ATM.

    • Keiji Okamoto
    • , Cristina Bartocci
    •  & Eros Lazzerini Denchi

  • Comment |

    A stark warning about the societal costs of stress comes from links between shortened telomeres, chronic stress and disease, say Elizabeth H. Blackburn and Elissa S. Epel.

    • Elizabeth H. Blackburn
    •  & Elissa S. Epel

  • Letter |

    The human CST complex is shown to interact with the telomeric primer and the POT1–TPP1 complex to inhibit telomerase activity in late S phase, thereby keeping unrestrained telomere lengthening in check.

    • Liuh-Yow Chen
    • , Sophie Redon
    •  & Joachim Lingner

  • Outlook |

    Elizabeth Blackburn gave the first lecture at the 2011 Lindau meeting, describing her Nobel prizewinning work on telomeres. These chromosomal caps are known to play a role in cancer and are implicated in ageing — but their full biological utility remains a mystery.

    • Michael Eisenstein

  • News Q&A |

    Telomeres may not predict how long we'll live, but they can still revolutionise medicine, says Nobel laureate Elizabeth Blackburn.

    • Jo Marchant

  • Letter |

    Two single-stranded DNA-binding proteins, POT1 and RPA, associate with telomeres. Binding of RPA to telomeres can activate a DNA damage response, so it was previously proposed that POT1 binds telomeres to prevent RPA association. Here, it is found that POT1–TPP1 cannot prevent RPA binding, and hnRNPA1 is identified as having this activity instead. In addition, it is shown that TERRA, a telomere-associated RNA, displaces hnRNPA1 and promotes POT1 binding after S phase, when replication is completed.

    • Rachel Litman Flynn
    • , Richard C. Centore
    •  & Lee Zou

  • Letter |

    Here it is shown that reactivation of endogenous telomerase activity in mice extends telomeres, reduces DNA damage signalling, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease and the reversal of damage observed here support the development of regenerative strategies designed to restore telomere integrity.

    • Mariela Jaskelioff
    • , Florian L. Muller
    •  & Ronald A. DePinho

  • Letter |

    The ends of chromosomes, known as telomeres, look like ends generated by double-strand breaks, but if treated as such the DNA damage repair system would initiate a checkpoint response and cause telomere–telomere fusions. These authors show that telomeres lack two types of histone modification that are required for recruitment of Crb2b53BP1, without which the checkpoint cannot be activated even if other DNA damage response proteins are recruited to a Taz1-deficient telomere.

    • Tiago Carneiro
    • , Lyne Khair
    •  & Miguel Godinho Ferreira

  • Letter |

    The ends of eukaryotic chromosomes are composed of repeat sequences known as telomeres. Various proteins bind telomeres to protect them from degradation or inappropriate DNA repair responses, and their length is maintained by a specialized reverse transcriptase, telomerase. These authors show that in the absence of telomerase, telomeres can be maintained by amplifying and recombining heterochromatin sequences there. This process requires histone methylation and two telomere-binding proteins, Pot1 and Ccq1.

    • Devanshi Jain
    • , Anna K. Hebden
    •  & Julia Promisel Cooper

  • Article |

    Zscan4 is shown to be involved in maintaining telomeres in embryonic stem (ES) cells. Only 5% of ES cells express Zscan4 at a given time, but nearly all ES cells activate Zscan4 at least once within nine passages. The transient Zscan4-positive state is associated with rapid telomere extension by telomere recombination and upregulation of meiosis–specific homologous recombination genes. Knocking down Zscan4 shortens telomeres, increases karyotype abnormalities and spontaneous sister chromatid exchange, and slows down cell proliferation until reaching crisis by eight passages.

    • Michal Zalzman
    • , Geppino Falco
    •  & Minoru S. H. Ko

  • Letter |

    Here, iPS cell technology is used to study the mechanisms underlying dyskeratosis congenita in humans. Reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting telomerase. The reprogrammed cells were able to overcome a critical limitation in telomerase RNA component (TERC) levels to restore telomere maintenance and self-renewal, and multiple telomerase components are targeted by pluripotency-associated transcription factors.

    • Suneet Agarwal
    • , Yuin-Han Loh
    •  & George Q. Daley

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