RAD27
S. cerevisiae
multifunctional nuclease RAD27
What the model saw
Gene: RAD27 Organism: Saccharomyces cerevisiae Known functions: multifunctional nuclease RAD27. 5'-3' exonuclease activity. 5'-flap endonuclease activity. DNA binding. catalytic activity. hydrolase activity, acting on ester bonds. magnesium ion binding. nuclease activity. protein binding.
View unredacted entry
multifunctional nuclease RAD27. 5'-3' exonuclease activity. 5'-flap endonuclease activity. DNA binding. catalytic activity. hydrolase activity, acting on ester bonds. magnesium ion binding. nuclease activity. protein binding.
Solver output
RAD27 (the yeast ortholog of human FEN1) encodes a structure-specific 5'-flap endonuclease and 5'-3' exonuclease that is essential for Okazaki fragment maturation during lagging-strand DNA replication. By cleaving 5'-flap intermediates generated during strand displacement synthesis, RAD27 ensures faithful completion of DNA replication and prevents the accumulation of unprocessed flap structures that would otherwise lead to repeat expansions, deletions, and gross chromosomal rearrangements. Loss of RAD27 in yeast causes elevated mutation rates, microsatellite instability, and increased DNA double-strand breaks, all hallmarks of genomic instability that accelerate aging. RAD27 also participates in long-patch base excision repair (BER), removing displaced 5'-flaps after gap-filling synthesis, thereby maintaining genome integrity against oxidative and spontaneous DNA damage. Its normal function thus directly suppresses the genomic instability hallmark of aging, making it a pro-longevity gene.
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 RAD27 as pro_longevity with high confidence (0.85). The mechanistic reasoning is excellent and accurate: RAD27/FEN1 is indeed a 5'-flap endonuclease critical for Okazaki fragment maturation and long-patch BER. The model correctly identifies that loss of RAD27 leads to genomic instability (elevated mutation rates, microsatellite instability, DSBs), which accelerates aging, making it a pro-longevity gene. All key pathways identified are correct and relevant.
Raw API responses
solver
{
"reasoning": "RAD27 (the yeast ortholog of human FEN1) encodes a structure-specific 5'-flap endonuclease and 5'-3' exonuclease that is essential for Okazaki fragment maturation during lagging-strand DNA replication. By cleaving 5'-flap intermediates generated during strand displacement synthesis, RAD27 ensures faithful completion of DNA replication and prevents the accumulation of unprocessed flap structures that would otherwise lead to repeat expansions, deletions, and gross chromosomal rearrangements. Loss of RAD27 in yeast causes elevated mutation rates, microsatellite instability, and increased DNA double-strand breaks, all hallmarks of genomic instability that accelerate aging. RAD27 also participates in long-patch base excision repair (BER), removing displaced 5'-flaps after gap-filling synthesis, thereby maintaining genome integrity against oxidative and spontaneous DNA damage. Its normal function thus directly suppresses the genomic instability hallmark of aging, making it a pro-longevity gene.",
"confidence": 0.85,
"key_pathways": [
"Okazaki fragment maturation / lagging-strand DNA replication",
"Base excision repair (long-patch BER)",
"DNA damage prevention / genomic stability maintenance"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted RAD27 as pro_longevity with high confidence (0.85). The mechanistic reasoning is excellent and accurate: RAD27/FEN1 is indeed a 5'-flap endonuclease critical for Okazaki fragment maturation and long-patch BER. The model correctly identifies that loss of RAD27 leads to genomic instability (elevated mutation rates, microsatellite instability, DSBs), which accelerates aging, making it a pro-longevity gene. All key pathways identified are correct and relevant.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}