Task Telomeric proteins in the radiation/DNA damage response (Completed)
Last Published:  11/23/20 11:55:12 AM (Central)
Short Title: Telomeric proteins
Responsible HRP Element: Space Radiation
Collaborating Org(s):
Funding Status: Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
Solicited
Aims:
Our overall aim is to study the effects of depleting expression of key telomeric binding proteins on DNA damage response/repair. The telomeric DNA-binding proteins TRF1 and TRF2 have multiple interacting binding partners, including TIN2, POT1 and tankyrase1. Many interactions between these players (and others) have been reported. Interestingly, TIN2 has recently been shown to have novel extra-telomeric functions in nuclear organization. Telomerase (hTERT) is also known to interact with many telomeric as well as non-telomeric proteins (including DNA repair proteins), and extra-curricular/pro-tumorigenic activities of telomerase independent of its classical role in telomere length maintenance - including enhanced repair - have been proposed, but remains an open issue. Our approach is to knockdown expression of these critical telomeric proteins in human cell lines utilizing siRNA strategies. DNA damage is induced by exposure to ionizing radiations (low LET gamma (gamma-rays or HZE 56Fe ions). We then employ a powerful combination of mutational analyses and cytogenetic approaches to examine the phenotypic and genotypic consequences of the telomeric deficiencies on DNA repair endpoints.
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