SAS3
S. cerevisiae
histone acetyltransferase
What the model saw
Gene: SAS3 Organism: Saccharomyces cerevisiae Known functions: histone acetyltransferase. chromatin binding. histone acetyltransferase activity. protein binding. protein-lysine-acetyltransferase activity. transcription coregulator activity. zinc ion binding.
View unredacted entry
histone acetyltransferase. chromatin binding. histone acetyltransferase activity. protein binding. protein-lysine-acetyltransferase activity. transcription coregulator activity. zinc ion binding.
Solver output
SAS3 encodes a MYST-family histone acetyltransferase (HAT) in S. cerevisiae that is the catalytic subunit of the NuA3 complex, primarily responsible for acetylating histone H3 at lysine 14 (H3K14ac). This mark is associated with active transcription and open chromatin states, which are critical for maintaining proper gene expression programs. Appropriate histone acetylation by SAS3/NuA3 helps preserve transcriptional fidelity and counteracts the age-associated drift toward aberrant silencing or derepression of chromatin domains. Loss of proper H3 acetylation is a hallmark of epigenetic dysregulation during aging, and HATs like SAS3 help maintain the youthful epigenetic landscape. Additionally, SAS3 functionally overlaps with GCN5 (the SAGA complex HAT), and the two together are essential for cell viability, underscoring the importance of this acetylation activity in sustaining normal cellular homeostasis and gene regulation that supports longevity.
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 predicted pro_longevity but the ground truth is anti_longevity. SAS3 is a histone acetyltransferase, and the model's reasoning that HAT activity generally supports longevity by maintaining epigenetic fidelity is plausible in general terms, but it gets the direction wrong for this specific gene. In yeast, SAS3 (as part of the NuA3 complex) can promote aging rather than extend lifespan - its deletion or loss may actually extend lifespan, making it anti-longevity. The model's reasoning about H3K14 acetylation maintaining a 'youthful epigenetic landscape' is speculative and not supported by the actual experimental evidence for SAS3 in yeast aging. The model had moderate confidence (0.62) but was still wrong on both the answer and the mechanistic interpretation. The reasoning quality is poor because it relies on generic HAT-longevity associations rather than SAS3-specific evidence.
Raw API responses
solver
{
"reasoning": "SAS3 encodes a MYST-family histone acetyltransferase (HAT) in S. cerevisiae that is the catalytic subunit of the NuA3 complex, primarily responsible for acetylating histone H3 at lysine 14 (H3K14ac). This mark is associated with active transcription and open chromatin states, which are critical for maintaining proper gene expression programs. Appropriate histone acetylation by SAS3/NuA3 helps preserve transcriptional fidelity and counteracts the age-associated drift toward aberrant silencing or derepression of chromatin domains. Loss of proper H3 acetylation is a hallmark of epigenetic dysregulation during aging, and HATs like SAS3 help maintain the youthful epigenetic landscape. Additionally, SAS3 functionally overlaps with GCN5 (the SAGA complex HAT), and the two together are essential for cell viability, underscoring the importance of this acetylation activity in sustaining normal cellular homeostasis and gene regulation that supports longevity.",
"confidence": 0.62,
"key_pathways": [
"NuA3 histone acetyltransferase complex / H3K14 acetylation",
"chromatin remodeling and transcriptional regulation",
"epigenetic maintenance of gene expression fidelity"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. SAS3 is a histone acetyltransferase, and the model's reasoning that HAT activity generally supports longevity by maintaining epigenetic fidelity is plausible in general terms, but it gets the direction wrong for this specific gene. In yeast, SAS3 (as part of the NuA3 complex) can promote aging rather than extend lifespan - its deletion or loss may actually extend lifespan, making it anti-longevity. The model's reasoning about H3K14 acetylation maintaining a 'youthful epigenetic landscape' is speculative and not supported by the actual experimental evidence for SAS3 in yeast aging. The model had moderate confidence (0.62) but was still wrong on both the answer and the mechanistic interpretation. The reasoning quality is poor because it relies on generic HAT-longevity associations rather than SAS3-specific evidence.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}