CDC26
S. cerevisiae
anaphase promoting complex subunit CDC26
What the model saw
Gene: CDC26 Organism: Saccharomyces cerevisiae Known functions: anaphase promoting complex subunit CDC26. ubiquitin protein ligase activity.
View unredacted entry
anaphase promoting complex subunit CDC26. ubiquitin protein ligase activity.
Solver output
CDC26 is a subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase that targets key cell cycle regulators (e.g., cyclins, securin) for proteasomal degradation to drive mitotic exit and G1 maintenance. While proper APC/C function is essential for genomic stability and preventing aberrant cell cycle progression — both of which are pro-longevity — CDC26 is a non-catalytic accessory subunit whose specific contribution to APC/C activity is modulatory rather than essential. Loss of APC/C function can lead to mitotic errors and genomic instability (anti-longevity), but overactivation can prematurely degrade mitotic regulators. The net longevity effect of CDC26 specifically is difficult to resolve because its role is structural/regulatory within the complex rather than a direct rate-limiting enzymatic step, and yeast longevity studies have not clearly assigned CDC26 as pro- or anti-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 "unclear" while the ground truth is "pro_longevity." The model's reasoning about CDC26's role in the APC/C is generally accurate (it is indeed a non-catalytic subunit of the APC/C), but the model failed to commit to the correct answer. The model expressed uncertainty about CDC26's longevity role, claiming yeast studies haven't clearly assigned it, when in fact GenAge classifies it as pro_longevity. The mechanism class of "cellular_senescence" is also questionable for a yeast gene — yeast don't undergo cellular senescence in the same way, and the more relevant mechanism would be cell cycle regulation/replicative aging. The model's hedging led to an incorrect final prediction despite having some relevant biological knowledge.
Raw API responses
solver
{
"reasoning": "CDC26 is a subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase that targets key cell cycle regulators (e.g., cyclins, securin) for proteasomal degradation to drive mitotic exit and G1 maintenance. While proper APC/C function is essential for genomic stability and preventing aberrant cell cycle progression — both of which are pro-longevity — CDC26 is a non-catalytic accessory subunit whose specific contribution to APC/C activity is modulatory rather than essential. Loss of APC/C function can lead to mitotic errors and genomic instability (anti-longevity), but overactivation can prematurely degrade mitotic regulators. The net longevity effect of CDC26 specifically is difficult to resolve because its role is structural/regulatory within the complex rather than a direct rate-limiting enzymatic step, and yeast longevity studies have not clearly assigned CDC26 as pro- or anti-longevity.",
"confidence": 0.42,
"key_pathways": [
"APC/C ubiquitin ligase complex",
"cell cycle regulation and mitotic exit",
"ubiquitin-proteasome system"
],
"mechanism_class": "cellular_senescence",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" while the ground truth is \"pro_longevity.\" The model's reasoning about CDC26's role in the APC/C is generally accurate (it is indeed a non-catalytic subunit of the APC/C), but the model failed to commit to the correct answer. The model expressed uncertainty about CDC26's longevity role, claiming yeast studies haven't clearly assigned it, when in fact GenAge classifies it as pro_longevity. The mechanism class of \"cellular_senescence\" is also questionable for a yeast gene — yeast don't undergo cellular senescence in the same way, and the more relevant mechanism would be cell cycle regulation/replicative aging. The model's hedging led to an incorrect final prediction despite having some relevant biological knowledge.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}