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Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
ATM activation by ionizing radiation requires BRCA1-associated BAAT1
Jason A Aglipay1, Sarah A Martin, Hideyuki Tawara
1Department of Oncological Sciences, Mount Sinai School of Medicine, New York University, New York, New York 10029, USA.
The Journal of Biological Chemistry
|February 3, 2006
Summary
The novel protein BAAT1 is crucial for activating ATM (ataxia telangiectasia mutated) after DNA damage. BAAT1
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- ATM (ataxia telangiectasia mutated) is essential for DNA double-strand break repair and cell cycle control.
- ATM activation by ionizing radiation (IR) involves phosphorylation at Ser1981.
- ATM-deficient cells exhibit extreme sensitivity to IR.
Purpose of the Study:
- To investigate the role of a novel BRCA1-associated protein, BAAT1, in ATM activation.
- To elucidate the mechanism by which BAAT1 regulates ATM activity.
- To understand the consequences of BAAT1 loss on DNA damage response.
Main Methods:
- Yeast two-hybrid screening to identify BAAT1.
- Small interfering RNA (siRNA) to deplete BAAT1.
- Western blotting to detect protein phosphorylation (ATM Ser1981, CHK2 Thr68).
- In vitro phosphatase assays using purified BAAT1 and Protein Phosphatase 2A (PP2A).
Main Results:
- BAAT1 binds to ATM and localizes to double-strand breaks.
- BAAT1 depletion reduces ATM Ser1981 and CHK2 Thr68 phosphorylation.
- BAAT1 regulates ATM phosphatase activity, potentially by inhibiting PP2A.
- Loss of BAAT1 leads to increased p53 and apoptosis.
Conclusions:
- DNA damage-induced ATM activation requires the coordinated assembly of BRCA1, BAAT1, and ATM.
- BAAT1 is a critical regulator of ATM activation and DNA damage response.
- BAAT1's role in ATM phosphatase regulation highlights a novel mechanism in DNA repair.
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