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Open AccessReview

Structural Features of Nucleoprotein CST/Shelterin Complex Involved in the Telomere Maintenance and Its Association with Disease Mutations

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Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
2
Department of Pharmacognosy College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, Saudi Arabia
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 359; https://doi.org/10.3390/cells9020359
Received: 13 December 2019 / Revised: 23 January 2020 / Accepted: 24 January 2020 / Published: 4 February 2020
(This article belongs to the Special Issue The Role of Telomere Biology in Aging and Human Disease 2020)
Telomere comprises the ends of eukaryotic linear chromosomes and is composed of G-rich (TTAGGG) tandem repeats which play an important role in maintaining genome stability, premature aging and onsets of many diseases. Majority of the telomere are replicated by conventional DNA replication, and only the last bit of the lagging strand is synthesized by telomerase (a reverse transcriptase). In addition to replication, telomere maintenance is principally carried out by two key complexes known as shelterin (TRF1, TRF2, TIN2, RAP1, POT1, and TPP1) and CST (CDC13/CTC1, STN1, and TEN1). Shelterin protects the telomere from DNA damage response (DDR) and regulates telomere length by telomerase; while, CST govern the extension of telomere by telomerase and C strand fill-in synthesis. We have investigated both structural and biochemical features of shelterin and CST complexes to get a clear understanding of their importance in the telomere maintenance. Further, we have analyzed ~115 clinically important mutations in both of the complexes. Association of such mutations with specific cellular fault unveils the importance of shelterin and CST complexes in the maintenance of genome stability. A possibility of targeting shelterin and CST by small molecule inhibitors is further investigated towards the therapeutic management of associated diseases. Overall, this review provides a possible direction to understand the mechanisms of telomere borne diseases, and their therapeutic intervention.
Keywords: telomere shortening; mutations; CST complex; shelterin complex; OB-fold proteins; structural genomics; cancer; Telomere replication; small molecule inhibitors telomere shortening; mutations; CST complex; shelterin complex; OB-fold proteins; structural genomics; cancer; Telomere replication; small molecule inhibitors
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MDPI and ACS Style

Amir, M.; Khan, P.; Queen, A.; Dohare, R.; Alajmi, M.F.; Hussain, A.; Islam, A.; Ahmad, F.; Hassan, I. Structural Features of Nucleoprotein CST/Shelterin Complex Involved in the Telomere Maintenance and Its Association with Disease Mutations. Cells 2020, 9, 359.

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