Ataxia telangiectasia mutated

An encyclopedia article about Ataxia telangiectasia mutated

Ataxia telangiectasia mutated (ATM) is a protein that plays a critical role in the cellular response to DNA damage. It is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. ATM is essential for maintaining genomic stability and preventing the development of cancer.

Function

ATM is a key regulator of the DNA damage response (DDR) pathway. Upon sensing DNA double-strand breaks, ATM is activated and phosphorylates several downstream targets, including the tumor suppressor protein p53, the checkpoint kinase CHK2, and the histone variant H2AX. These phosphorylation events lead to cell cycle arrest, allowing the cell time to repair the DNA damage. If the damage is irreparable, ATM can also initiate apoptosis to prevent the propagation of damaged DNA.

Clinical Significance

Mutations in the ATM gene can lead to a rare genetic disorder known as ataxia-telangiectasia (A-T). This condition is characterized by progressive neurological degeneration, immunodeficiency, and a predisposition to cancer, particularly leukemia and lymphoma. Patients with A-T exhibit increased sensitivity to ionizing radiation due to impaired DNA repair mechanisms.

ATM is also implicated in the development of breast cancer and other malignancies. Heterozygous carriers of ATM mutations have an increased risk of developing breast cancer, highlighting the importance of ATM in tumor suppression.

Research and Therapeutic Implications

Research into ATM and its role in the DDR has significant implications for cancer therapy. Inhibitors of ATM are being explored as potential treatments to sensitize cancer cells to radiation therapy and chemotherapy. By inhibiting ATM, cancer cells with defective DNA repair pathways can be selectively targeted, sparing normal cells.

Also see

• DNA repair
• Ataxia-telangiectasia
• Tumor suppressor gene
• Cell cycle checkpoint
• Apoptosis