PNC1
S. cerevisiae
nicotinamidase
What the model saw
Gene: PNC1 Organism: Saccharomyces cerevisiae Known functions: nicotinamidase. nicotinamidase activity. zinc ion binding.
View unredacted entry
nicotinamidase. nicotinamidase activity. zinc ion binding.
Solver output
PNC1 encodes the yeast nicotinamidase, which converts nicotinamide (NAM) to nicotinic acid, the first step in the NAD+ salvage pathway. This reaction is critical because nicotinamide is a potent inhibitor of Sir2 (the yeast sirtuin), a key NAD+-dependent deacetylase that promotes longevity by silencing repetitive DNA elements and regulating stress responses. By depleting intracellular nicotinamide, PNC1 relieves Sir2 inhibition and simultaneously feeds into NAD+ biosynthesis, boosting Sir2 activity. PNC1 expression is upregulated by caloric restriction and other longevity-extending interventions, placing it as a central mediator of CR-induced lifespan extension in yeast. Loss of PNC1 shortens replicative lifespan, while overexpression extends it in a Sir2-dependent manner, firmly establishing its pro-longevity role through the NAD+/sirtuin axis.
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 identified PNC1 as pro-longevity with high confidence (0.92). The mechanistic reasoning is excellent and accurate: PNC1 encodes nicotinamidase, which converts nicotinamide to nicotinic acid, relieving Sir2 inhibition and boosting NAD+ biosynthesis. The model correctly notes that PNC1 is upregulated by caloric restriction, that overexpression extends replicative lifespan in a Sir2-dependent manner, and that loss of PNC1 shortens lifespan. All key details align with the well-established literature on PNC1 in yeast longevity (Anderson et al., 2003).
Raw API responses
solver
{
"reasoning": "PNC1 encodes the yeast nicotinamidase, which converts nicotinamide (NAM) to nicotinic acid, the first step in the NAD+ salvage pathway. This reaction is critical because nicotinamide is a potent inhibitor of Sir2 (the yeast sirtuin), a key NAD+-dependent deacetylase that promotes longevity by silencing repetitive DNA elements and regulating stress responses. By depleting intracellular nicotinamide, PNC1 relieves Sir2 inhibition and simultaneously feeds into NAD+ biosynthesis, boosting Sir2 activity. PNC1 expression is upregulated by caloric restriction and other longevity-extending interventions, placing it as a central mediator of CR-induced lifespan extension in yeast. Loss of PNC1 shortens replicative lifespan, while overexpression extends it in a Sir2-dependent manner, firmly establishing its pro-longevity role through the NAD+/sirtuin axis.",
"confidence": 0.92,
"key_pathways": [
"NAD+ salvage pathway",
"Sir2/sirtuin deacetylase activation",
"caloric restriction signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified PNC1 as pro-longevity with high confidence (0.92). The mechanistic reasoning is excellent and accurate: PNC1 encodes nicotinamidase, which converts nicotinamide to nicotinic acid, relieving Sir2 inhibition and boosting NAD+ biosynthesis. The model correctly notes that PNC1 is upregulated by caloric restriction, that overexpression extends replicative lifespan in a Sir2-dependent manner, and that loss of PNC1 shortens lifespan. All key details align with the well-established literature on PNC1 in yeast longevity (Anderson et al., 2003).",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}