SWI5

S. cerevisiae

DNA-binding transcription factor SWI5

What the model saw

Gene: SWI5
Organism: Saccharomyces cerevisiae
Known functions: DNA-binding transcription factor SWI5. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II transcription regulatory region sequence-specific DNA binding. mediator complex binding. sequence-specific DNA binding. transcription cis-regulatory region binding. zinc ion binding.

View unredacted entry

DNA-binding transcription factor SWI5. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II transcription regulatory region sequence-specific DNA binding. mediator complex binding. sequence-specific DNA binding. transcription cis-regulatory region binding. zinc ion binding.

Solver output

Predicted influence

Pro-longevity

Confidence

62%

Mechanism

Cellular senescence

Reasoning

SWI5 is a zinc-finger transcription factor that activates RNA Pol II-dependent transcription of key target genes in S. cerevisiae, most notably HO (mating-type switching) and genes involved in cell cycle exit and DNA damage response. Critically, SWI5 directly activates transcription of SIC1, the CDK inhibitor that enforces G1 arrest and proper cell cycle progression, and also drives expression of genes involved in DNA repair (e.g., RAD5 pathway components). By ensuring timely CDK inhibition via SIC1 and coordinating DNA damage responses, SWI5 promotes genomic integrity and orderly cell cycle control. Loss of SWI5 function impairs these transcriptional programs, leading to genomic instability and aberrant cell cycle progression, which are associated with accelerated aging phenotypes in yeast. The mediator complex binding further supports its role as a broad transcriptional activator of stress-response and cell cycle regulatory genes relevant to replicative lifespan.

Key pathways

SIC1-mediated CDK inhibition and G1/S cell cycle controlDNA damage response transcription (RAD pathway activation)Mediator complex-dependent RNA Pol II transcriptional regulation

Longevity influence

Anti-longevity

Lifespan effect

Increase

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

Answer

✗Incorrect

Mechanism

✗Incorrect

Reasoning quality

2/5

Failure mode

Confident wrong

Notes

The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about SWI5 activating SIC1 and DNA repair genes is partially accurate in terms of known SWI5 biology, but the conclusion drawn (that this makes SWI5 pro-longevity) is incorrect. In reality, SWI5 is anti-longevity in yeast - likely because its role in promoting HO endonuclease expression and mating-type switching, or other transcriptional programs, shortens lifespan rather than extending it. The model constructed a plausible-sounding but ultimately incorrect mechanistic narrative, and had moderate confidence (0.62) in the wrong direction.

Raw API responses

solver

{
  "reasoning": "SWI5 is a zinc-finger transcription factor that activates RNA Pol II-dependent transcription of key target genes in S. cerevisiae, most notably HO (mating-type switching) and genes involved in cell cycle exit and DNA damage response. Critically, SWI5 directly activates transcription of SIC1, the CDK inhibitor that enforces G1 arrest and proper cell cycle progression, and also drives expression of genes involved in DNA repair (e.g., RAD5 pathway components). By ensuring timely CDK inhibition via SIC1 and coordinating DNA damage responses, SWI5 promotes genomic integrity and orderly cell cycle control. Loss of SWI5 function impairs these transcriptional programs, leading to genomic instability and aberrant cell cycle progression, which are associated with accelerated aging phenotypes in yeast. The mediator complex binding further supports its role as a broad transcriptional activator of stress-response and cell cycle regulatory genes relevant to replicative lifespan.",
  "confidence": 0.62,
  "key_pathways": [
    "SIC1-mediated CDK inhibition and G1/S cell cycle control",
    "DNA damage response transcription (RAD pathway activation)",
    "Mediator complex-dependent RNA Pol II transcriptional regulation"
  ],
  "mechanism_class": "cellular_senescence",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about SWI5 activating SIC1 and DNA repair genes is partially accurate in terms of known SWI5 biology, but the conclusion drawn (that this makes SWI5 pro-longevity) is incorrect. In reality, SWI5 is anti-longevity in yeast - likely because its role in promoting HO endonuclease expression and mating-type switching, or other transcriptional programs, shortens lifespan rather than extending it. The model constructed a plausible-sounding but ultimately incorrect mechanistic narrative, and had moderate confidence (0.62) in the wrong direction.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}