RT Journal Article
SR Electronic
T1 Telomere-loop dynamics in chromosome end protection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 279877
DO 10.1101/279877
A1 Van Ly, David
A1 Jie Low, Ronnie Ren
A1 Frölich, Sonja
A1 Bartolec, Tara K.
A1 Kafer, Georgia R.
A1 Pickett, Hilda A.
A1 Gaus, Katharina
A1 Cesare, Anthony J.
YR 2018
UL http://biorxiv.org/content/early/2018/03/09/279877.abstract
AB 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.