Question 1

What does ATM do?

Accepted Answer

ATM is a master serine/threonine kinase activated by DNA double-strand breaks through the MRN complex (MRE11–RAD50–NBS1). Once active, it phosphorylates hundreds of substrates including H2AX, CHK2, BRCA1, and p53 to simultaneously activate DNA repair pathways and impose cell cycle checkpoints.

Question 2

What disease is caused by ATM mutations?

Accepted Answer

Germline ATM mutations cause ataxia-telangiectasia (A-T), a rare autosomal recessive syndrome characterised by progressive cerebellar ataxia, oculocutaneous telangiectasias, immune deficiency, radiation hypersensitivity, and dramatically elevated cancer risk — particularly lymphomas and leukaemias.

Question 3

What is ATM's role in cancer?

Accepted Answer

Somatic ATM mutations occur in ~15% of chronic lymphocytic leukaemias, mantle cell lymphoma, and prostate cancer. ATM loss impairs DNA damage response, allowing cells to accumulate mutations and also sensitising tumours to DNA-damaging chemotherapy and PARP inhibitors.

Question 4

How does ATM activate p53?

Accepted Answer

ATM phosphorylates p53 at serine-15, disrupting its interaction with MDM2 and preventing ubiquitin-mediated degradation. ATM also phosphorylates CHK2, which reinforces p53 stabilisation through serine-20 phosphorylation. This kinase relay ensures rapid, robust p53 activation within minutes of DNA damage.

ATM Gene Function

Overview

More Tumor Suppressor Genes