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Telomere-loop dynamics in chromosome end protection

By David Van Ly, Ronnie Ren Jie Low, Sonja Frölich, Tara K Bartolec, Georgia R. Kafer, Hilda A. Pickett, Katharina Gaus, Anthony J Cesare

Posted 09 Mar 2018
bioRxiv DOI: 10.1101/279877 (published DOI: 10.1016/j.molcel.2018.06.025)

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.

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