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.
| Original language | English |
|---|---|
| Pages (from-to) | 709-720 |
| Number of pages | 12 |
| Journal | Cell |
| Volume | 127 |
| Issue number | 4 |
| DOIs | |
| State | Published - Nov 17 2006 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
The DNA Damage Machinery and Homologous Recombination Pathway Act Consecutively to Protect Human Telomeres. / Verdun, Ramiro E; Karlseder, Jan.
In: Cell, Vol. 127, No. 4, 17.11.2006, p. 709-720.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The DNA Damage Machinery and Homologous Recombination Pathway Act Consecutively to Protect Human Telomeres
AU - Verdun, Ramiro E
AU - Karlseder, Jan
PY - 2006/11/17
Y1 - 2006/11/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33750801681&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750801681&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2006.09.034
DO - 10.1016/j.cell.2006.09.034
M3 - Article
C2 - 17110331
AN - SCOPUS:33750801681
VL - 127
SP - 709
EP - 720
JO - Cell
JF - Cell
SN - 0092-8674
IS - 4
ER -