| First Author | Van Ly D | Year | 2018 |
| Journal | Mol Cell | Volume | 71 |
| Issue | 4 | Pages | 510-525.e6 |
| PubMed ID | 30033372 | Mgi Jnum | J:266445 |
| Mgi Id | MGI:6202197 | Doi | 10.1016/j.molcel.2018.06.025 |
| Citation | Van Ly D, et al. (2018) Telomere Loop Dynamics in Chromosome End Protection. Mol Cell 71(4):510-525.e6 |
| abstractText | 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. |
