ISW1
S. cerevisiae
chromatin-remodeling ATPase ISW1
What the model saw
Gene: ISW1 Organism: Saccharomyces cerevisiae Known functions: chromatin-remodeling ATPase ISW1. ATP binding. ATP hydrolysis activity. DNA binding. chromatin binding. mRNA 3'-UTR binding. nucleosome array spacer activity. nucleosome binding. protein binding. rDNA binding. transcription cis-regulatory region binding.
View unredacted entry
chromatin-remodeling ATPase ISW1. ATP binding. ATP hydrolysis activity. DNA binding. chromatin binding. mRNA 3'-UTR binding. nucleosome array spacer activity. nucleosome binding. protein binding. rDNA binding. transcription cis-regulatory region binding.
Solver output
ISW1 encodes the catalytic ATPase subunit of the ISWI chromatin-remodeling complex in S. cerevisiae, which uses ATP hydrolysis to space nucleosome arrays and regulate chromatin architecture. Proper nucleosome positioning by ISW1 suppresses cryptic transcription initiation and maintains transcriptional fidelity, both of which deteriorate with age. ISW1's rDNA binding activity is particularly relevant, as it helps maintain repressive chromatin at the rDNA locus, suppressing the formation of extrachromosomal rDNA circles (ERCs), a well-established driver of replicative aging in yeast. Additionally, ISW1-mediated nucleosome spacing supports epigenetic stability and prevents the age-associated loss of heterochromatin that contributes to genomic instability. Loss of ISW1 function has been associated with shortened replicative lifespan, consistent with a pro-longevity role through maintenance of chromatin organization and rDNA silencing.
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 ISW1 as pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning about ISW1 maintaining rDNA silencing and suppressing ERCs is plausible-sounding but incorrect — in reality, ISW1 deletion extends lifespan in yeast, making it anti-longevity. The model fabricated the claim that "loss of ISW1 function has been associated with shortened replicative lifespan," which is the opposite of what the data shows. The mechanistic reasoning about chromatin remodeling and rDNA is directionally wrong in its conclusion. This is a confident wrong answer with hallucinated specifics supporting the incorrect direction.
Raw API responses
solver
{
"reasoning": "ISW1 encodes the catalytic ATPase subunit of the ISWI chromatin-remodeling complex in S. cerevisiae, which uses ATP hydrolysis to space nucleosome arrays and regulate chromatin architecture. Proper nucleosome positioning by ISW1 suppresses cryptic transcription initiation and maintains transcriptional fidelity, both of which deteriorate with age. ISW1's rDNA binding activity is particularly relevant, as it helps maintain repressive chromatin at the rDNA locus, suppressing the formation of extrachromosomal rDNA circles (ERCs), a well-established driver of replicative aging in yeast. Additionally, ISW1-mediated nucleosome spacing supports epigenetic stability and prevents the age-associated loss of heterochromatin that contributes to genomic instability. Loss of ISW1 function has been associated with shortened replicative lifespan, consistent with a pro-longevity role through maintenance of chromatin organization and rDNA silencing.",
"confidence": 0.72,
"key_pathways": [
"rDNA chromatin silencing and ERC suppression",
"nucleosome spacing and transcriptional fidelity",
"ISWI chromatin remodeling complex activity"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted ISW1 as pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning about ISW1 maintaining rDNA silencing and suppressing ERCs is plausible-sounding but incorrect — in reality, ISW1 deletion extends lifespan in yeast, making it anti-longevity. The model fabricated the claim that \"loss of ISW1 function has been associated with shortened replicative lifespan,\" which is the opposite of what the data shows. The mechanistic reasoning about chromatin remodeling and rDNA is directionally wrong in its conclusion. This is a confident wrong answer with hallucinated specifics supporting the incorrect direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}