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Telomere-loop dynamics in chromosome end protection
David Van Ly,
Ronnie Ren Jie Low,
Tara K Bartolec,
Georgia R. Kafer,
Hilda A. Pickett,
Anthony J Cesare
Posted 09 Mar 2018
bioRxiv DOI: 10.1101/279877 (published DOI: 10.1016/j.molcel.2018.06.025)
Posted 09 Mar 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.
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