HDA1
S. cerevisiae
histone deacetylase HDA1
What the model saw
Gene: HDA1 Organism: Saccharomyces cerevisiae Known functions: histone deacetylase HDA1. chromatin binding. histone deacetylase activity. histone deacetylase activity, hydrolytic mechanism. identical protein binding. protein binding. zinc ion binding.
View unredacted entry
histone deacetylase HDA1. chromatin binding. histone deacetylase activity. histone deacetylase activity, hydrolytic mechanism. identical protein binding. protein binding. zinc ion binding.
Solver output
HDA1 encodes a class II histone deacetylase (HDAC) in S. cerevisiae that removes acetyl groups from histones H3 and H2B, promoting chromatin compaction and transcriptional silencing. Histone deacetylation by HDA1 contributes to epigenetic reprogramming that can silence stress-response and longevity-promoting genes. In yeast replicative and chronological aging models, HDAC activity — particularly by Sir2 and related deacetylases — is tightly regulated; however, HDA1 specifically has been shown to antagonize longevity, as its deletion extends chronological lifespan, likely by relieving repression of genes involved in stress resistance and metabolic adaptation. The zinc-dependent hydrolytic deacetylase mechanism places HDA1 in the RPD3/HDA1 superfamily, where its activity on chromatin reduces transcriptional plasticity needed to cope with aging-associated stressors. Thus, the normal function of HDA1 opposes longevity by enforcing a repressive chromatin state that limits adaptive gene expression during aging.
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 HDA1 as anti_longevity, matching the ground truth. The mechanistic reasoning is sound: HDA1 is a class II histone deacetylase whose deletion extends lifespan (chronological lifespan in yeast), consistent with its anti-longevity classification. The model correctly identifies the epigenetic mechanism (chromatin compaction, transcriptional silencing of stress-response genes) and places HDA1 in the RPD3/HDA1 superfamily. The reasoning is well-grounded in yeast aging biology. Confidence of 0.72 is appropriate given the specificity of the claim about HDA1 vs. other HDACs.
Raw API responses
solver
{
"reasoning": "HDA1 encodes a class II histone deacetylase (HDAC) in S. cerevisiae that removes acetyl groups from histones H3 and H2B, promoting chromatin compaction and transcriptional silencing. Histone deacetylation by HDA1 contributes to epigenetic reprogramming that can silence stress-response and longevity-promoting genes. In yeast replicative and chronological aging models, HDAC activity — particularly by Sir2 and related deacetylases — is tightly regulated; however, HDA1 specifically has been shown to antagonize longevity, as its deletion extends chronological lifespan, likely by relieving repression of genes involved in stress resistance and metabolic adaptation. The zinc-dependent hydrolytic deacetylase mechanism places HDA1 in the RPD3/HDA1 superfamily, where its activity on chromatin reduces transcriptional plasticity needed to cope with aging-associated stressors. Thus, the normal function of HDA1 opposes longevity by enforcing a repressive chromatin state that limits adaptive gene expression during aging.",
"confidence": 0.72,
"key_pathways": [
"histone deacetylation / chromatin remodeling",
"epigenetic gene silencing",
"stress response transcriptional regulation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted HDA1 as anti_longevity, matching the ground truth. The mechanistic reasoning is sound: HDA1 is a class II histone deacetylase whose deletion extends lifespan (chronological lifespan in yeast), consistent with its anti-longevity classification. The model correctly identifies the epigenetic mechanism (chromatin compaction, transcriptional silencing of stress-response genes) and places HDA1 in the RPD3/HDA1 superfamily. The reasoning is well-grounded in yeast aging biology. Confidence of 0.72 is appropriate given the specificity of the claim about HDA1 vs. other HDACs.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}