Journal article
CTC1 deletion results in defective telomere replication, leading to catastrophic telomere loss and stem cell exhaustion
The EMBO journal, Vol.31(10), pp.2309-2321
05/16/2012
Handle:
https://hdl.handle.net/2376/104337
PMCID: PMC3364752
PMID: 22531781
Abstract
Mouse knockout analysis of CTC1, part of the telomeric RPA-like CST complex in mammals and recently found mutated in human ‘Coats plus' disease, reveals its key role in telomere replication rather than telomere protection.
The proper maintenance of telomeres is essential for genome stability. Mammalian telomere maintenance is governed by a number of telomere binding proteins, including the newly identified CTC1–STN1–TEN1 (CST) complex. However, the
in vivo
functions of mammalian CST remain unclear. To address this question, we conditionally deleted
CTC1
from mice. We report here that
CTC1
null mice experience rapid onset of global cellular proliferative defects and die prematurely from complete bone marrow failure due to the activation of an ATR-dependent G2/M checkpoint. Acute deletion of
CTC1
does not result in telomere deprotection, suggesting that mammalian CST is not involved in capping telomeres. Rather, CTC1 facilitates telomere replication by promoting efficient restart of stalled replication forks.
CTC1
deletion results in increased loss of leading C-strand telomeres, catastrophic telomere loss and accumulation of excessive ss telomere DNA. Our data demonstrate an essential role for CTC1 in promoting efficient replication and length maintenance of telomeres.
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Details
- Title
- CTC1 deletion results in defective telomere replication, leading to catastrophic telomere loss and stem cell exhaustion
- Creators
- Peili Gu - , New Haven, CTJin-Na Min - , New Haven, CTYang Wang - , New Haven, CTChenhui Huang - , Spokane, WATao Peng - , Houston, TXWeihang Chai - , Spokane, WASandy Chang - , New Haven, CT
- Publication Details
- The EMBO journal, Vol.31(10), pp.2309-2321
- Academic Unit
- UNKNOWN
- Publisher
- Nature Publishing Group
- Identifiers
- 99900546689901842
- Language
- English
- Resource Type
- Journal article