期刊
MOLECULAR CELL
卷 61, 期 2, 页码 274-286出版社
CELL PRESS
DOI: 10.1016/j.molcel.2015.12.009
关键词
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资金
- ARC
- Conseil General 06 de la Region Provence Alpes-Cote d'Azur
- FEDER
- le Minitere de l'Enseignement Superieur
- la region Provence Alpes-Cote d'Azur
- l'INSERM
- Fondation ARC
- Ligue Contre le Cancer (EG Equipe labellise)
- ANR (Teloloop'') [ANR-1582-30020690]
- Institut Nationale du Cancer (INCa) (TELOCHROM)
- Investments for the Future'' LABEX SIGNALIFE [ANR-11-LABX-0028-01]
- NIH [NIH R01GM107559]
The shelterin proteins protect telomeres against activation of the DNA damage checkpoints and recombinational repair. We show here that a dimer of the shelterin subunit TRF2 wraps similar to 90 bp of DNA through several lysine and arginine residues localized around its homodimerization domain. The expression of a wrapping-deficient TRF2 mutant, named Top-less, alters telomeric DNA topology, decreases the number of terminal loops (t-loops), and triggers the ATM checkpoint, while still protecting telomeres against non-homologous end joining (NHEJ). In Top-less cells, the protection against NHEJ is alleviated if the expression of the TRF2-interacting protein RAP1 is reduced. We conclude that a distinctive topological state of telomeric DNA, controlled by the TRF2-dependent DNA wrapping and linked to t-loop formation, inhibits both ATM activation and NHEJ. The presence of RAP1 at telomeres appears as a backup mechanism to prevent NHEJ when topology-mediated telomere protection is impaired.
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