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Type: Journal article
Title: Telomere loop dynamics in chromosome end protection
Author: Van Ly, D.
Low, R.
Frolich, S.
Bartolec, T.
Kafer, G.
Pickett, H.
Gaus, K.
Cesare, A.
Citation: Molecular Cell, 2018; 71(4):510-525
Publisher: Cell Press
Issue Date: 2018
ISSN: 1097-2765
Statement of
David Van Ly, Ronnie Ren Jie Low, Sonja Frölich, Tara K.Bartolec, Georgia R.Kafer, Hilda A.Pickett, Katharina Gaus, Anthony J.Cesare
Abstract: Telomeres regulate DNA damage response (DDR) and DNA repair activity at chromosome ends. How telomere macromolecular structure contributes to ATM regulation and its potential dissociation from control over non-homologous end joining (NHEJ)-dependent telomere fusion is of central importance to telomere-dependent cell aging and tumor suppression. Using super-resolution microscopy, we identify that ATM activation at mammalian telomeres with reduced TRF2 or at human telomeres during mitotic arrest occurs specifically with a structural change from telomere loops (t-loops) to linearized telomeres. Additionally, we find the TRFH domain of TRF2 regulates t-loop formation while suppressing ATM activity. Notably, we demonstrate that ATM activation and telomere linearity occur separately from telomere fusion via NHEJ and 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 specifically regulate ATM activation independent of telomere mechanisms to inhibit NHEJ.
Keywords: ATM
Aurora B kinase
DNA damage response
non-homologous end joining
super-resolution microscopy
telomere loops
telomere protection
Rights: © 2018 Elsevier Inc.
DOI: 10.1016/j.molcel.2018.06.025
Grant ID:
Appears in Collections:Aurora harvest 8
Genetics publications

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