ATM adenovirus

Ataxia-telangiectasia mutated (ATM) protein is a large serine/threonine protein kinase and a core regulator of the DNA damage response, particularly crucial for DNA double-strand breaks. ATM belongs to the phosphatidylinositol 3-kinase-related kinase (PIKK) family and is rapidly recruited to damage sites via the MRE11–RAD50–NBS1 (MRN) complex. It is activated through autophosphorylation and other regulatory mechanisms (e.g., acetylation). Once activated, ATM phosphorylates numerous substrates, including p53, CHK2, H2AX, BRCA1, KAP1, and MDM2, thereby establishing cell cycle checkpoints in G1/S, S phase, and G2/M phases, coordinating DNA repair pathways, and promoting apoptosis or senescence when necessary. Beyond its classic genome maintenance functions, ATM is also involved in multiple aspects of oxidative stress signaling, redox homeostasis, mitochondrial function, and metabolic regulation.

The ATM adenovirus is a first-generation replication-deficient Ad5 backbone virus with deletions in the E1/E3 regions, expressing human ATM under the control of the cytomegalovirus (CMV) immediate early promoter and containing a 6xHN tag at the C-terminus. This vector is designed for efficient, transient, and episomal expression in various mammalian cell types without genomic integration, enabling controllable gain-of-function studies of the ATM signaling pathway. The viral vector is available in versions corresponding to the classic A-T complementation groups A, C, and D, allowing for direct functional complementation studies in ATM-deficient models. This enables researchers to rescue or reconstitute specific phenotypes and compare how different allelic types affect checkpoint control, DNA repair fidelity, radiosensitivity, and genomic stability. The strong CMV promoter supports high-level expression suitable for pathway studies, while the C-terminal 6xHN tag facilitates detection, enrichment, and interaction studies using specific antibodies, enabling experiments such as Western blotting, immunoprecipitation, and proteomic analysis of ATM-associated complexes.