| The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres |
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| Author(s): Verdun RE (Verdun, Ramiro E.), Karlseder J (Karlseder, Jan) |
| Source: CELL Volume: 127 Issue: 4 Pages: 709-720 Published: NOV 17 2006 |
| Times Cited: 81 References: 68 |
| Abstract: Telomeres protect chromosome ends from being detected as lesions and from triggering DNA damage checkpoints. Paradoxically, telomere function depends on checkpoint proteins such as ATM and ATR, but a molecular model explaining this seemingly contradictory relationship has been missing so far. Here we show that the DNA damage machinery acts on telomeres in at least two independent steps. First, the ATR-dependent machinery is recruited to telomeres before telomere replication is completed, likely in response to single-stranded DNA resulting from replication fork stalling. Second, after replication, telomeres attract ATM and the homologous recombination (HR) machinery. In vivo and in vitro results suggest that the HR machinery is required for formation of a telomere-specific structure at chromosome ends after replication. Our results suggest that telomere ends need to be recognized as DNA damage to complete end replication and to acquire a structure that is essential for function. |
| Document Type: Article |
| Language: English |
| Reprint Address: Karlseder, J (reprint author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA |
Addresses:
1. Salk Inst Biol Studies, La Jolla, CA 92037 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 109TB |
| ISSN: 0092-8674 |
| DOI: 10.1016/j.cell.2006.09.034 |