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TRF2 and lamin A/C interact to facilitate the functional organization of chromosome ends

Author

Listed:
  • Ashley M. Wood

    (Feinberg School of Medicine, Northwestern University)

  • Jannie M. Rendtlew Danielsen

    (Fred Hutchinson Cancer Research Center
    Present address: Department of Disease Biology, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen, Denmark)

  • Catherine A. Lucas

    (Feinberg School of Medicine, Northwestern University)

  • Ellen L. Rice

    (Feinberg School of Medicine, Northwestern University)

  • David Scalzo

    (Fred Hutchinson Cancer Research Center)

  • Takeshi Shimi

    (Feinberg School of Medicine, Northwestern University)

  • Robert D. Goldman

    (Feinberg School of Medicine, Northwestern University)

  • Erica D. Smith

    (Feinberg School of Medicine, Northwestern University)

  • Michelle M. Le Beau

    (Section of Hematology/Oncology, The University of Chicago)

  • Steven T. Kosak

    (Feinberg School of Medicine, Northwestern University)

Abstract

Telomeres protect the ends of linear genomes, and the gradual loss of telomeres is associated with cellular ageing. Telomere protection involves the insertion of the 3′ overhang facilitated by telomere repeat-binding factor 2 (TRF2) into telomeric DNA, forming t-loops. We present evidence suggesting that t-loops can also form at interstitial telomeric sequences in a TRF2-dependent manner, forming an interstitial t-loop (ITL). We demonstrate that TRF2 association with interstitial telomeric sequences is stabilized by co-localization with A-type lamins (lamin A/C). We also find that lamin A/C interacts with TRF2 and that reduction in levels of lamin A/C or mutations in LMNA that cause an autosomal dominant premature ageing disorder—Hutchinson Gilford Progeria Syndrome (HGPS)—lead to reduced ITL formation and telomere loss. We propose that cellular and organismal ageing are intertwined through the effects of the interaction between TRF2 and lamin A/C on chromosome structure.

Suggested Citation

  • Ashley M. Wood & Jannie M. Rendtlew Danielsen & Catherine A. Lucas & Ellen L. Rice & David Scalzo & Takeshi Shimi & Robert D. Goldman & Erica D. Smith & Michelle M. Le Beau & Steven T. Kosak, 2014. "TRF2 and lamin A/C interact to facilitate the functional organization of chromosome ends," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6467
    DOI: 10.1038/ncomms6467
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    Cited by:

    1. Wei Jin & Shaoshuai Jiang & Xinyi Liu & Yi He & Tuo Li & Jingchun Ma & Zhihong Chen & Xiaomei Lu & Xinguang Liu & Weinian Shou & Guoxiang Jin & Junjun Ding & Zhongjun Zhou, 2024. "Disorganized chromatin hierarchy and stem cell aging in a male patient of atypical laminopathy-based progeria mandibuloacral dysplasia type A," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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