Ercc2
M. musculus
excision repair cross-complementing rodent repair deficiency, complementation group 2
What the model saw
Gene: Ercc2 Organism: Mus musculus Known functions: excision repair cross-complementing rodent repair deficiency, complementation group 2. general transcription and DNA repair factor IIH helicase subunit XPD. 5'-3' DNA helicase activity. ATP binding. ATP hydrolysis activity. DNA binding. DNA helicase activity. damaged DNA binding. helicase activity. hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides. nucleic acid binding. protein-macromolecule adaptor activity.
View unredacted entry
excision repair cross-complementing rodent repair deficiency, complementation group 2. general transcription and DNA repair factor IIH helicase subunit XPD. 5'-3' DNA helicase activity. ATP binding. ATP hydrolysis activity. DNA binding. DNA helicase activity. damaged DNA binding. helicase activity. hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides. nucleic acid binding. protein-macromolecule adaptor activity.
Solver output
Ercc2 encodes XPD, the 5'-to-3' DNA helicase subunit of the TFIIH complex, which is essential for nucleotide excision repair (NER). By unwinding DNA at sites of helix-distorting lesions (e.g., UV-induced pyrimidine dimers, bulky adducts), XPD enables accurate excision and resynthesis, thereby suppressing the accumulation of somatic mutations and DNA damage over time. Loss-of-function mutations in Ercc2/XPD in mice cause accelerated aging phenotypes (progeroid syndromes), directly demonstrating that its normal activity opposes genomic instability—a primary hallmark of aging. Additionally, XPD's role in TFIIH links it to transcription-coupled NER, protecting actively transcribed genes from damage-induced stalling and cell death. The ATP-dependent helicase activity is the molecular engine driving damage recognition and strand separation in the NER pathway.
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 Ercc2/XPD in mice. The mechanistic reasoning is excellent and accurate: XPD is the helicase subunit of TFIIH involved in nucleotide excision repair (NER), and loss-of-function mutations cause progeroid (accelerated aging) phenotypes in mice, confirming its pro-longevity role. The model correctly identifies the genomic instability mechanism, the TFIIH complex involvement, transcription-coupled NER, and the ATP-dependent helicase activity. High confidence (0.88) is appropriate given the well-established biology.
Raw API responses
solver
{
"reasoning": "Ercc2 encodes XPD, the 5'-to-3' DNA helicase subunit of the TFIIH complex, which is essential for nucleotide excision repair (NER). By unwinding DNA at sites of helix-distorting lesions (e.g., UV-induced pyrimidine dimers, bulky adducts), XPD enables accurate excision and resynthesis, thereby suppressing the accumulation of somatic mutations and DNA damage over time. Loss-of-function mutations in Ercc2/XPD in mice cause accelerated aging phenotypes (progeroid syndromes), directly demonstrating that its normal activity opposes genomic instability—a primary hallmark of aging. Additionally, XPD's role in TFIIH links it to transcription-coupled NER, protecting actively transcribed genes from damage-induced stalling and cell death. The ATP-dependent helicase activity is the molecular engine driving damage recognition and strand separation in the NER pathway.",
"confidence": 0.88,
"key_pathways": [
"nucleotide excision repair (NER)",
"TFIIH complex / transcription-coupled repair",
"DNA damage response"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Ercc2/XPD in mice. The mechanistic reasoning is excellent and accurate: XPD is the helicase subunit of TFIIH involved in nucleotide excision repair (NER), and loss-of-function mutations cause progeroid (accelerated aging) phenotypes in mice, confirming its pro-longevity role. The model correctly identifies the genomic instability mechanism, the TFIIH complex involvement, transcription-coupled NER, and the ATP-dependent helicase activity. High confidence (0.88) is appropriate given the well-established biology.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}