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ATM function and telomere stability
1Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York, NY 10032, USA. tpl1@columbia.edu
Abstract:
Accumulation of DNA damage has been associated with the onset of senescence and predisposition to cancer. The gene responsible for ataxia telangiectasia (A-T) is ATM (ataxia-telangiectasia mutant), a master controller of cellular pathways and networks, orchestrating the responses to a specific type of DNA damage: the double strand break. Based on the homology of the human ATM gene to the TEL1, MEC1 and rad3 genes of yeast, it has now been demonstrated that mutations in ATM lead to defective telomere maintenance in mammalian cells. While ATM has both nuclear and cytoplasmic functions, this review will focus on its roles in telomere metabolism and how ATM and telomeres serve as controllers of cellular responses to DNA damage.
Insights
The ataxia-telangiectasia mutated (ATM) gene controls cellular responses to DNA damage. Mutations in ATM disrupt telomere maintenance, impacting senescence and cancer risk.
Area of Science:
- Genetics
- Molecular Biology
- Cellular Biology
Background:
- DNA damage accumulation is linked to cellular senescence and cancer development.
- The ataxia-telangiectasia mutated (ATM) gene is crucial for managing DNA double-strand break responses.
- ATM exhibits both nuclear and cytoplasmic functions within cells.
Purpose of the Study:
- To review the role of ATM in telomere metabolism.
- To explore how ATM and telomeres regulate cellular responses to DNA damage.
Main Methods:
- Comparative genomics analysis of ATM homologs in yeast (TEL1, MEC1, rad3).
- Investigation of ATM's function in telomere maintenance in mammalian cells.
- Literature review focusing on ATM's nuclear and cytoplasmic roles in DNA damage response.
Main Results:
- Mutations in the ATM gene lead to impaired telomere maintenance in mammalian cells.
- ATM plays a significant role in regulating telomere stability.
- ATM and telomeres act as key controllers in cellular DNA damage response pathways.
Conclusions:
- ATM is essential for proper telomere maintenance.
- Dysfunctional ATM and telomeres can contribute to senescence and cancer predisposition.
- Understanding ATM's role in telomere metabolism is vital for comprehending DNA damage responses.