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Updated: Jun 16, 2026
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Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
Published on: May 22, 2013
ATR contributes to telomere maintenance in human cells
Gaëlle Pennarun1, Françoise Hoffschir, Deborah Revaud
1CEA/DSV/iRCM/SCSR, Laboratoire de Radiopathologie, INSERM-Université Paris VII U967, 92265 Fontenay-aux-Roses, France.
Nucleic Acids Research
|February 12, 2010
Summary
Ataxia telangiectasia and Rad3-related (ATR) deficiency causes telomere instability in human cells, leading to sister telomere fusions and chromatid aberrations during replication. This highlights ATR's critical role in maintaining telomere integrity.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Telomere maintenance is crucial for genomic stability, involving DNA replication and repair proteins.
- The kinase ATR is vital for genome integrity across eukaryotes, but its role in mammalian telomere maintenance is unclear.
Purpose of the Study:
- To investigate the role of ATR in telomere maintenance in human cells.
- To characterize telomere aberrations caused by ATR deficiency.
Main Methods:
- Telomere-fluorescence in situ hybridization (Telo-FISH) on metaphase chromosomes.
- Chromosome orientation-FISH (CO-FISH) to analyze leading and lagging strand telomeres.
- Assessment of ATR-deficient human fibroblasts (Seckel syndrome) and HeLa cells.
Main Results:
- ATR deficiency leads to significant telomere instability, including sister telomere fusions and chromatid-type aberrations.
- These aberrations occur during or after telomere replication, affecting both leading and lagging strands.
- ATR deficiency sensitizes cells to G-quadruplex ligand 360A, exacerbating telomere aberrations, particularly on lagging strands.
Conclusions:
- ATR plays a critical role in human telomere maintenance, especially during and after telomere replication.
- ATR deficiency compromises telomere stability, contributing to genomic instability.
- The findings provide new insights into the mechanisms of telomere maintenance and the function of ATR.
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