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Expression of Telomere-Associated Proteins is Interdependent to Stabilize Native Telomere Structure and Telomere Dysfunction by G-Quadruplex Ligand Causes TERRA Upregulation

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Abstract

Telomere DNA can form specialized nucleoprotein structure with telomere-associated proteins to hide free DNA ends or G-quadruplex structures under certain conditions especially in presence of G-quadruplex ligand. Telomere DNA is transcribed to form non-coding telomere repeat-containing RNA (TERRA) whose biogenesis and function is poorly understood. Our aim was to find the role of telomere-associated proteins and telomere structures in TERRA transcription. We silenced four [two shelterin (TRF1, TRF2) and two non-shelterin (PARP-1, SLX4)] telomere-associated genes using siRNA and verified depletion in protein level. Knocking down of one gene modulated expression of other telomere-associated genes and increased TERRA from 10q, 15q, XpYp and XqYq chromosomes in A549 cells. Telomere was destabilized or damaged by G-quadruplex ligand pyridostatin (PDS) and bleomycin. Telomere dysfunction-induced foci (TIFs) were observed for each case of depletion of proteins, treatment with PDS or bleomycin. TERRA level was elevated by PDS and bleomycin treatment alone or in combination with depletion of telomere-associated proteins.

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Acknowledgements

U.G. is grateful to DBT, New Delhi, India (BT/PR 4809/BRB/10/1028/2012) for providing financial assistance and infrastructural facility. P.C. thanks to ICMR, New Delhi, India, for her fellowship (BMS/FW/CMB/2015-24000/JUN-2016/05/WB/GOVT). S.G. thanks to DBT, New Delhi, India, for his fellowship. R.S. is thankful to University of Kalyani for URS fellowship. U.G. is also grateful to DST, New Delhi, India (SR/SO/BB-0017/2010) for partial financial assistance.

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    1. Department of Biochemistry & Biophysics, University of Kalyani, Kalyani, 741235, India

      Ratan Sadhukhan, Priyanka Chowdhury, Sourav Ghosh & Utpal Ghosh

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    Ratan Sadhukhan and Priyanka Chowdhury contributed equally to this work.

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    Sadhukhan, R., Chowdhury, P., Ghosh, S. et al. Expression of Telomere-Associated Proteins is Interdependent to Stabilize Native Telomere Structure and Telomere Dysfunction by G-Quadruplex Ligand Causes TERRA Upregulation. Cell Biochem Biophys 76, 311–319 (2018). https://doi.org/10.1007/s12013-017-0835-0

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