Question

Ataxia telangiectasia (OMIM 208900) is a human inherited disorder characterized by poor coordination (ataxia), red marks on the face (telangiectasia), increased sensitivity to X-rays and other radiation, and an increased susceptibility to cancer. Recent studies have shown that this disorder occurs as a result of mutation of the ATM gene.

Propose a mechanism for how a mutation in the ATM gene leads to the characteristics associated with the disorder.

a) ATM is a protein kinase that is activated in response to DNA damage and then activates proteins of the DNA ultraviolet (UV) repair system.
b) ATM is a protein kinase that is activated in response to DNA damage and then activates other proteins that cause cell cycle arrest and/or apoptosis.
c) ATM is a protein kinase that is a part of signal transduction pathway that blocks apoptosis and activates DNA polymerases.
d) ATM is a part of a check point in the cell cycle before S phase. In the absence of ATM, DNA replication is blocked.

Answer 1

The ATM gene mutation leads to ataxia telangiectasia by disrupting the cellular response to DNA damage, leading to accumulated errors, cell cycle dysregulation, and increased cancer risk.

Step-by-step explanation:

Ataxia telangiectasia is a disorder caused by mutations in the ATM gene, which is crucial for DNA repair and cell cycle regulation. The ATM protein, a kinase, is activated in response to DNA damage and phosphorylates a number of proteins involved in repairing DNA and maintaining integrity during cell replication. The proposed mechanism B is the most accurate: ATM is a protein kinase that is activated in response to DNA damage and then activates other proteins that cause cell cycle arrest and/or apoptosis.

When the ATM gene is mutated, its important role in the response to DNA damage is compromised. Normally, ATM would activate repair systems or trigger cell cycle arrest to prevent propagation of the damage. Without functional ATM, errors accumulate in the DNA, leading to a heightened risk of cancer due to unregulated cell growth and division. Problems in coordination and other characteristics of ataxia telangiectasia arise from cellular dysfunction and death, partly due to these unchecked DNA damages.

In summary, a dysfunctional ATM protein leads to poor coordination of DNA repair mechanisms, allowing the accumulation of DNA damage, disruptions in the cell cycle, and an increase in cancer susceptibility. This aligns with the cellular and molecular pathology observed in patients with ataxia telangiectasia.