Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential

Cancers
Stina George FernandesEkta Khattar

Abstract

Telomeres are the ends of linear chromosomes comprised of repetitive nucleotide sequences in humans. Telomeres preserve chromosomal stability and genomic integrity. Telomere length shortens with every cell division in somatic cells, eventually resulting in replicative senescence once telomere length becomes critically short. Telomere shortening can be overcome by telomerase enzyme activity that is undetectable in somatic cells, while being active in germline cells, stem cells, and immune cells. Telomeres are bound by a shelterin complex that regulates telomere lengthening as well as protects them from being identified as DNA damage sites. Telomeres are transcribed by RNA polymerase II, and generate a long noncoding RNA called telomeric repeat-containing RNA (TERRA), which plays a key role in regulating subtelomeric gene expression. Replicative immortality and genome instability are hallmarks of cancer and to attain them cancer cells exploit telomere maintenance and telomere protection mechanisms. Thus, understanding the role of telomeres and their associated proteins in cancer initiation, progression and treatment is very important. The present review highlights the critical role of various telomeric components with recently es...Continue Reading

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Citations

Nov 1, 2020·Cells·Christian T StackhouseChristopher D Willey
Jan 16, 2021·Cell·Deepavali ChakravartiRonald A DePinho
Feb 19, 2021·Cellular and Molecular Life Sciences : CMLS·Semih Can AkincilarVinay Tergaonkar
Mar 18, 2021·International Journal of Biological Macromolecules·Xu-Hui ZhuHeng Luo

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Methods Mentioned

BETA
xenograft
flow cytometry
transfection

Clinical Trials Mentioned

NCT02719977
NCT02293707
NCT01789099
NCT03538314
NCT02275416

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