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|Title:||HARNESSING A SECONDARY DNA STRUCTURE AT THE TELOMERES USING A SMALL MOLECULE, TMPYP4: IMPLICATION IN CANCER THERAPY||Authors:||SHRIRAM VENKATESAN||Keywords:||Telomere, Telomerase, Cancer, Glioblastoma Multiforme, DNA repair, DNA damage||Issue Date:||30-Sep-2013||Citation:||SHRIRAM VENKATESAN (2013-09-30). HARNESSING A SECONDARY DNA STRUCTURE AT THE TELOMERES USING A SMALL MOLECULE, TMPYP4: IMPLICATION IN CANCER THERAPY. ScholarBank@NUS Repository.||Abstract:||During carcinogenesis, cells encounter phases of potentially catastrophic genetic instability and telomere crisis; hence surviving cancer cells invariably possess terrific telomere maintenance and DNA repair mechanisms. In almost all cancers, the cells activate an otherwise mostly repressed enzyme ? telomerase, which interacts with the telomere dynamically and elongates it. Disrupting telomere homeostasis thus becomes important, and stabilisation of secondary structures at the telomeres has been shown to be a promising strategy. Previous studies involving G-quadruplex stabilising agents have revealed cancer-specific effects. This study investigates the potency of one such small molecule, TMPyP4, in human brain cancer cells ?medulloblastoma and glioblastoma multiforme. Comprehensive biological studies on its effect on telomeres is lacking. The study shows that TMPyP4 reduces telomerase activity, causes telomere shortening and telomere dysfunction, eventually leading to mitotic catastrophe in the cancer cells. TMPyP4 has promising properties as a cancer drug and as a tool to study telomere biology.||URI:||http://scholarbank.nus.edu.sg/handle/10635/50221|
|Appears in Collections:||Ph.D Theses (Open)|
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