FOB1
S. cerevisiae
replication fork barrier binding protein FOB1
What the model saw
Gene: FOB1 Organism: Saccharomyces cerevisiae Known functions: replication fork barrier binding protein FOB1. rDNA spacer replication fork barrier binding. zinc ion binding.
View unredacted entry
replication fork barrier binding protein FOB1. rDNA spacer replication fork barrier binding. zinc ion binding.
Solver output
FOB1 binds the rDNA spacer replication fork barrier (RFB), stalling replication forks at the rDNA locus. This stalling promotes recombination between rDNA repeats, generating extrachromosomal rDNA circles (ERCs). ERCs accumulate asymmetrically in mother cells during yeast aging and are a well-established driver of replicative aging in S. cerevisiae. Deletion of FOB1 dramatically reduces ERC accumulation and extends replicative lifespan, demonstrating that FOB1's normal function is pro-aging. The zinc ion binding activity supports its structural role in sequence-specific DNA binding at the RFB site, enabling fork arrest and subsequent recombination events that destabilize the rDNA locus.
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 FOB1 as anti_longevity with high confidence (0.92). The mechanistic reasoning is excellent and accurate: FOB1 stalls replication forks at the rDNA locus, promoting recombination and ERC formation, which accumulate in mother cells and drive replicative aging. The model correctly notes that FOB1 deletion reduces ERC accumulation and extends lifespan. This is well-established biology (Defossez et al., 1999). The zinc ion binding role in structural DNA binding is also correctly contextualized.
Raw API responses
solver
{
"reasoning": "FOB1 binds the rDNA spacer replication fork barrier (RFB), stalling replication forks at the rDNA locus. This stalling promotes recombination between rDNA repeats, generating extrachromosomal rDNA circles (ERCs). ERCs accumulate asymmetrically in mother cells during yeast aging and are a well-established driver of replicative aging in S. cerevisiae. Deletion of FOB1 dramatically reduces ERC accumulation and extends replicative lifespan, demonstrating that FOB1's normal function is pro-aging. The zinc ion binding activity supports its structural role in sequence-specific DNA binding at the RFB site, enabling fork arrest and subsequent recombination events that destabilize the rDNA locus.",
"confidence": 0.92,
"key_pathways": [
"rDNA replication fork barrier",
"extrachromosomal rDNA circle (ERC) formation",
"rDNA recombination"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identified FOB1 as anti_longevity with high confidence (0.92). The mechanistic reasoning is excellent and accurate: FOB1 stalls replication forks at the rDNA locus, promoting recombination and ERC formation, which accumulate in mother cells and drive replicative aging. The model correctly notes that FOB1 deletion reduces ERC accumulation and extends lifespan. This is well-established biology (Defossez et al., 1999). The zinc ion binding role in structural DNA binding is also correctly contextualized.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}