Topors
M. musculus
topoisomerase I binding, arginine/serine-rich
What the model saw
Gene: Topors Organism: Mus musculus Known functions: topoisomerase I binding, arginine/serine-rich. E3 ubiquitin-protein ligase Topors. DNA binding. DNA topoisomerase binding. SUMO transferase activity. antigen binding. metal ion binding. protein binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity.
View unredacted entry
topoisomerase I binding, arginine/serine-rich. E3 ubiquitin-protein ligase Topors. DNA binding. DNA topoisomerase binding. SUMO transferase activity. antigen binding. metal ion binding. protein binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity.
Solver output
Topors functions as both an E3 ubiquitin ligase and a SUMO E3 ligase (SUMO transferase activity), and directly binds DNA topoisomerase I. These dual activities place Topors at the intersection of DNA damage response and genome maintenance: ubiquitin-mediated degradation of damaged or stalled topoisomerase I complexes prevents persistent DNA strand breaks, while SUMOylation of target proteins (including p53) modulates DNA repair and transcriptional stress responses. By resolving topoisomerase I-DNA cleavage complexes and facilitating SUMOylation-dependent DNA repair signaling, Topors helps maintain genomic integrity. Loss of such genome surveillance activity is a canonical driver of accelerated aging through the hallmark of genomic instability. Its arginine/serine-rich domain further suggests roles in RNA processing and splicing-associated genome protection.
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 pro_longevity for Topors. The mechanistic reasoning is plausible and internally consistent - Topors as an E3 ubiquitin ligase and SUMO transferase involved in DNA damage response and genome maintenance is a reasonable explanation for pro-longevity effects. However, the reasoning is somewhat speculative and generic (genomic instability is a common fallback for DNA-related genes). The confidence of 0.62 is appropriately moderate. The mechanism cannot be fully verified without seeing the actual GenAge curation notes, but the logic is sound given the known functions listed.
Raw API responses
solver
{
"reasoning": "Topors functions as both an E3 ubiquitin ligase and a SUMO E3 ligase (SUMO transferase activity), and directly binds DNA topoisomerase I. These dual activities place Topors at the intersection of DNA damage response and genome maintenance: ubiquitin-mediated degradation of damaged or stalled topoisomerase I complexes prevents persistent DNA strand breaks, while SUMOylation of target proteins (including p53) modulates DNA repair and transcriptional stress responses. By resolving topoisomerase I-DNA cleavage complexes and facilitating SUMOylation-dependent DNA repair signaling, Topors helps maintain genomic integrity. Loss of such genome surveillance activity is a canonical driver of accelerated aging through the hallmark of genomic instability. Its arginine/serine-rich domain further suggests roles in RNA processing and splicing-associated genome protection.",
"confidence": 0.62,
"key_pathways": [
"DNA damage response / topoisomerase I cleavage complex resolution",
"E3 ubiquitin-proteasome pathway (genome surveillance)",
"SUMOylation signaling (p53 and DNA repair regulation)"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Topors. The mechanistic reasoning is plausible and internally consistent - Topors as an E3 ubiquitin ligase and SUMO transferase involved in DNA damage response and genome maintenance is a reasonable explanation for pro-longevity effects. However, the reasoning is somewhat speculative and generic (genomic instability is a common fallback for DNA-related genes). The confidence of 0.62 is appropriately moderate. The mechanism cannot be fully verified without seeing the actual GenAge curation notes, but the logic is sound given the known functions listed.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}