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https://hdl.handle.net/2440/117579
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Type: | Journal article |
Title: | Telomere loop dynamics in chromosome end protection |
Author: | Van Ly, D. Low, R.R.J. Frolich, S. Bartolec, T.K. Kafer, G.R. Pickett, H.A. Gaus, K. Cesare, A.J. |
Citation: | Molecular Cell, 2018; 71(4):510-525 |
Publisher: | Cell Press |
Issue Date: | 2018 |
ISSN: | 1097-2765 1097-4164 |
Statement of Responsibility: | 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 TRF2 mitosis non-homologous end joining super-resolution microscopy telomere loops telomere protection telomeres |
Rights: | © 2018 Elsevier Inc. |
DOI: | 10.1016/j.molcel.2018.06.025 |
Grant ID: | http://purl.org/au-research/grants/arc/CE140100011 http://purl.org/au-research/grants/arc/LP140100967 http://purl.org/au-research/grants/arc/LE150100163 http://purl.org/au-research/grants/nhmrc/1059278 http://purl.org/au-research/grants/nhmrc/1037320 http://purl.org/au-research/grants/nhmrc/1053195 http://purl.org/au-research/grants/nhmrc/1106241 http://purl.org/au-research/grants/nhmrc/1104461 |
Published version: | http://dx.doi.org/10.1016/j.molcel.2018.06.025 |
Appears in Collections: | Aurora harvest 8 Genetics publications |
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