Unfolding of Telomere’s Loop Leads the Oxidative Damage Within DNA – A Breakthrough In Telomere Based Anti-aging Research (2018)

We used super-resolution microscopy to investigate the role of macromolecular telomere structure in chromosome end protection. In murine and human cells with reduced TRF2, we find that ATM-activation at chromosome ends occurs with a structural change from t-loops to linearized chromosome ends through t-loop unfolding. Comparably, we find Aurora B kinase regulates telomere linearity concurrent with ATM activation at telomeres during mitotic arrest. Using a separation of function allele, we find that the TRFH domain of TRF2 regulates t-loop formation while suppressing ATM activity. Notably, we demonstrate that telomere linearity and ATM activation occur separately from telomere fusion via non-homologous end-joining (NHEJ). Further, we show that linear DDR-positive telomeres can remain resistant to fusion, even during an extended G1-arrest when NHEJ is most active. Collectively, these results suggest t-loops act as conformational switches that regulate ATM activation at chromosome ends independent of mechanisms to suppress chromosome end fusion.


About Robert Zinn

Robert Zinn, M.D., Ph.D. is a medical doctor, physician, and web entrepreneur, who, for over 15 years was employed by academic and research institutions and focused his clinical practices on very specialized patient populations, such as those with rare genetic diseases or rare cancers. He shares his knowledge through his website, NutritionTheory.org

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