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The RNA-binding protein RALY promotes ATM activation by stabilizing Tip60
Bo Yao1, Kailiang Zhao2, Ning Yu1
1Department of Thoracic Surgery, The First Affiliated Hospital of USTC, National Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Oncogene
|July 21, 2026
Summary
The RNA-binding protein RALY stabilizes Tip60, a key ATM activator, by preventing its degradation. This RALY-Tip60 interaction is crucial for DNA damage response and suggests RALY as a cancer radiosensitivity target.
Area of Science:
- Molecular Biology
- Cellular Biology
- Cancer Research
Background:
- Maintaining genome integrity relies on rapid DNA damage response (DDR) and repair.
- ATM kinase is central to DDR signaling and DNA repair after double-strand breaks (DSBs).
- The exact mechanisms of ATM activation are not fully understood.
Purpose of the Study:
- To identify novel regulators of ATM activation.
- To elucidate the molecular mechanisms controlling ATM activation.
- To explore RALY's role in DNA repair and cancer radiosensitivity.
Main Methods:
- Co-immunoprecipitation assays to detect protein interactions.
- Western blotting to assess protein stability and ubiquitination.
- Cellular assays to evaluate DNA repair capacity and radiosensitivity.
Main Results:
- RALY directly binds and stabilizes Tip60, a crucial ATM activator.
- RALY inhibits Mdm2-mediated degradation of Tip60 by competing for Mdm2 binding.
- RALY inhibition impairs ATM activation, DNA repair, and increases cancer cell radiosensitivity.
Conclusions:
- RALY is a novel regulator of ATM activation through Tip60 stabilization.
- RALY plays a critical role in DNA damage response and genome integrity.
- RALY represents a potential therapeutic target for enhancing cancer radiosensitivity.
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