Journal article
Telomere Loop Dynamics in Chromosome End Protection
Molecular Cell, Vol.71(4), pp.510-525.e6
2018
PMID: 30033372
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.
Details
- Title
- Telomere Loop Dynamics in Chromosome End Protection
- Authors
- David Van Ly (Author) - University of SydneyRonnie Ren Jie Low (Author) - University of SydneySonja Frölich (Author) - University of SydneyTara K Bartolec (Author) - University of SydneyGeorgia R Kafer (Author) - University of SydneyHilda A Pickett (Author) - University of SydneyKatharina Gaus (Author) - UNSW AustraliaAnthony J Cesare (Author) - University of Sydney
- Publication details
- Molecular Cell, Vol.71(4), pp.510-525.e6
- Publisher
- Cell Press
- DOI
- 10.1016/j.molcel.2018.06.025
- ISSN
- 1097-4164
- PMID
- 30033372
- Organisation Unit
- Centre for Bioinnovation; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy; University of the Sunshine Coast, Queensland; School of Health - Biomedicine; Australian Centre for Pacific Islands Research
- Language
- English
- Record Identifier
- 99554708502621
- Output Type
- Journal article
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- Domestic collaboration
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
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Source: InCites