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Influence of ATM function on telomere metabolism
L B Smilenov1, S E Morgan, W Mellado
1Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Oncogene
|December 24, 1997
Summary
The ATM gene product influences telomere metabolism, affecting telomeric associations and telomere length in cancer cells. Manipulating ATM function reveals its role in maintaining telomere stability.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- The ATM gene product is crucial for DNA repair and cell cycle control, with defects leading to ataxia telangiectasia (A-T).
- ATM shares homology with yeast TEL1, implicated in telomere maintenance, suggesting a potential role for ATM in telomere metabolism.
Purpose of the Study:
- To investigate the role of the ATM gene product in human telomere metabolism.
- To examine the effects of manipulating ATM function on telomeric associations, telomere length, and telomerase activity.
Main Methods:
- Utilized human RKO colorectal tumor cells and SV40-transformed fibroblasts from A-T patients.
- Expressed dominant-negative or complementing ATM gene fragments in these cells.
- Assessed telomeric associations (TA), telomere length, and telomerase activity.
Main Results:
- RKO cells expressing ATM fragments showed increased TA and shortened telomeres, mimicking A-T phenotypes.
- Dominant-negative ATM expression enhanced TA frequency after gamma irradiation.
- Fibroblasts from A-T patients expressing a complementing ATM fragment exhibited reduced TA.
Conclusions:
- The ATM gene product plays a significant role in regulating telomere metabolism.
- ATM function is linked to telomeric associations and telomere length maintenance.
- These findings highlight ATM's involvement in genomic stability through telomere regulation.