Atm
M. musculus
ataxia telangiectasia mutated
What the model saw
Gene: Atm Organism: Mus musculus Known functions: ataxia telangiectasia mutated. serine-protein kinase ATM. 1-phosphatidylinositol-3-kinase activity. DNA-dependent protein kinase activity. histone H2AXS139 kinase activity. identical protein binding. kinase activity. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity. protein-containing complex binding.
View unredacted entry
ataxia telangiectasia mutated. serine-protein kinase ATM. 1-phosphatidylinositol-3-kinase activity. DNA-dependent protein kinase activity. histone H2AXS139 kinase activity. identical protein binding. kinase activity. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity. protein-containing complex binding.
Solver output
ATM (Ataxia Telangiectasia Mutated) is a master regulator of the DNA damage response (DDR), functioning as a serine/threonine kinase that is activated by DNA double-strand breaks. Its hallmark activity — phosphorylation of histone H2AX at Ser139 (γH2AX) — initiates the recruitment of DNA repair machinery at break sites, enabling faithful repair of double-strand breaks via homologous recombination and non-homologous end joining. By coordinating cell cycle checkpoints (through phosphorylation of CHK2, p53, BRCA1, and other substrates) and facilitating DNA repair, ATM suppresses the accumulation of genomic damage that drives aging-associated pathologies. Loss of ATM in mice leads to premature aging phenotypes, neurodegeneration, cancer predisposition, and shortened lifespan, consistent with its role in counteracting genomic instability — a primary hallmark of aging. Its PI3K-like kinase activity also contributes to broader stress-response signaling, further supporting cellular homeostasis under genotoxic stress.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly predicted ATM as pro_longevity with high confidence (0.85). The mechanistic reasoning is excellent and accurate: ATM is indeed a master regulator of the DNA damage response, and loss of ATM in mice leads to premature aging phenotypes and shortened lifespan. The model correctly identified the key pathways (H2AX phosphorylation, CHK2/p53 checkpoint signaling, genomic stability) and correctly linked ATM's function to the genomic instability hallmark of aging. The reasoning is thorough, well-supported, and mechanistically sound.
Raw API responses
solver
{
"reasoning": "ATM (Ataxia Telangiectasia Mutated) is a master regulator of the DNA damage response (DDR), functioning as a serine/threonine kinase that is activated by DNA double-strand breaks. Its hallmark activity — phosphorylation of histone H2AX at Ser139 (γH2AX) — initiates the recruitment of DNA repair machinery at break sites, enabling faithful repair of double-strand breaks via homologous recombination and non-homologous end joining. By coordinating cell cycle checkpoints (through phosphorylation of CHK2, p53, BRCA1, and other substrates) and facilitating DNA repair, ATM suppresses the accumulation of genomic damage that drives aging-associated pathologies. Loss of ATM in mice leads to premature aging phenotypes, neurodegeneration, cancer predisposition, and shortened lifespan, consistent with its role in counteracting genomic instability — a primary hallmark of aging. Its PI3K-like kinase activity also contributes to broader stress-response signaling, further supporting cellular homeostasis under genotoxic stress.",
"confidence": 0.85,
"key_pathways": [
"DNA double-strand break repair (DDR/H2AX phosphorylation)",
"Cell cycle checkpoint signaling (CHK2/p53 axis)",
"Genomic stability maintenance"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted ATM as pro_longevity with high confidence (0.85). The mechanistic reasoning is excellent and accurate: ATM is indeed a master regulator of the DNA damage response, and loss of ATM in mice leads to premature aging phenotypes and shortened lifespan. The model correctly identified the key pathways (H2AX phosphorylation, CHK2/p53 checkpoint signaling, genomic stability) and correctly linked ATM's function to the genomic instability hallmark of aging. The reasoning is thorough, well-supported, and mechanistically sound.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}