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CTCF driven TERRA transcription facilitates completion of telomere DNA replication

Author

Listed:
  • Kate Beishline

    (The Wistar Institute
    Bloomsburg University)

  • Olga Vladimirova

    (The Wistar Institute)

  • Stephen Tutton

    (The Wistar Institute)

  • Zhuo Wang

    (The Wistar Institute)

  • Zhong Deng

    (The Wistar Institute)

  • Paul M. Lieberman

    (The Wistar Institute)

Abstract

Telomere repeat DNA forms a nucleo-protein structure that can obstruct chromosomal DNA replication, especially under conditions of replication stress. Transcription of telomere repeats can initiate at subtelomeric CTCF-binding sites to generate telomere repeat-encoding RNA (TERRA), but the role of transcription, CTCF, and TERRA in telomere replication is not known. Here, we have used CRISPR/Cas9 gene editing to mutate CTCF-binding sites at the putative start site of TERRA transcripts for a class of subtelomeres. Under replication stress, telomeres lacking CTCF-driven TERRA exhibit sister-telomere loss and upon entry into mitosis, exhibit the formation of ultra-fine anaphase bridges and micronuclei. Importantly, these phenotypes could be rescued by the forced transcription of TERRA independent of CTCF binding. Our findings indicate that subtelomeric CTCF facilitates telomeric DNA replication by promoting TERRA transcription. Our findings also demonstrate that CTCF-driven TERRA transcription acts in cis to facilitate telomere repeat replication and chromosome stability.

Suggested Citation

  • Kate Beishline & Olga Vladimirova & Stephen Tutton & Zhuo Wang & Zhong Deng & Paul M. Lieberman, 2017. "CTCF driven TERRA transcription facilitates completion of telomere DNA replication," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02212-w
    DOI: 10.1038/s41467-017-02212-w
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    Cited by:

    1. Meng Xu & Dulmi Senanayaka & Rongwei Zhao & Tafadzwa Chigumira & Astha Tripathi & Jason Tones & Rachel M. Lackner & Anne R. Wondisford & Laurel N. Moneysmith & Alexander Hirschi & Sara Craig & Sahar A, 2024. "TERRA-LSD1 phase separation promotes R-loop formation for telomere maintenance in ALT cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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