Msh2
M. musculus
mutS homolog 2
What the model saw
Gene: Msh2 Organism: Mus musculus Known functions: mutS homolog 2. DNA mismatch repair protein Msh2. ADP binding. ATP binding. ATP hydrolysis activity. ATP-dependent DNA damage sensor activity. ATP-dependent activity, acting on DNA. DNA binding. MutLalpha complex binding. centromeric DNA binding. chromatin binding. damaged DNA binding. dinucleotide insertion or deletion binding. dinucleotide repeat insertion binding. double-stranded DNA binding. enzyme activator activity. four-way junction DNA binding. guanine/thymine mispair binding. magnesium ion binding. mismatched DNA binding. oxidized purine DNA binding. protein homodimerization activity. single guanine insertion binding. single thymine insertion binding. single-stranded DNA binding.
View unredacted entry
mutS homolog 2. DNA mismatch repair protein Msh2. ADP binding. ATP binding. ATP hydrolysis activity. ATP-dependent DNA damage sensor activity. ATP-dependent activity, acting on DNA. DNA binding. MutLalpha complex binding. centromeric DNA binding. chromatin binding. damaged DNA binding. dinucleotide insertion or deletion binding. dinucleotide repeat insertion binding. double-stranded DNA binding. enzyme activator activity. four-way junction DNA binding. guanine/thymine mispair binding. magnesium ion binding. mismatched DNA binding. oxidized purine DNA binding. protein homodimerization activity. single guanine insertion binding. single thymine insertion binding. single-stranded DNA binding.
Solver output
Msh2 is a core component of the DNA mismatch repair (MMR) system, forming the MutSα heterodimer (with Msh6) or MutSβ (with Msh3) to recognize and bind mismatched bases, insertion/deletion loops, and oxidized purines in DNA. Its ATP-dependent DNA damage sensor activity initiates the MMR cascade by recruiting MutLα, ultimately excising and correcting replication errors. Loss of Msh2 in mice leads to microsatellite instability, accelerated tumor formation, and shortened lifespan, demonstrating that its normal function suppresses genomic instability. By maintaining replication fidelity and correcting oxidative DNA lesions (e.g., 8-oxoguanine mispairs), Msh2 directly counteracts the accumulation of somatic mutations that drive aging-associated pathologies. This places Msh2 squarely within the genomic instability hallmark of aging as a pro-longevity factor.
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 Msh2 in Mus musculus with high confidence (0.92). The mechanistic reasoning is accurate and detailed: Msh2 is indeed a core MMR component, its loss leads to microsatellite instability, accelerated tumorigenesis, and shortened lifespan in mice. The model correctly identifies the genomic instability hallmark of aging as the relevant mechanism, and accurately describes the MutSα/MutSβ heterodimer formation, MutLα recruitment, and oxidized purine recognition. All key pathways cited are correct and relevant.
Raw API responses
solver
{
"reasoning": "Msh2 is a core component of the DNA mismatch repair (MMR) system, forming the MutSα heterodimer (with Msh6) or MutSβ (with Msh3) to recognize and bind mismatched bases, insertion/deletion loops, and oxidized purines in DNA. Its ATP-dependent DNA damage sensor activity initiates the MMR cascade by recruiting MutLα, ultimately excising and correcting replication errors. Loss of Msh2 in mice leads to microsatellite instability, accelerated tumor formation, and shortened lifespan, demonstrating that its normal function suppresses genomic instability. By maintaining replication fidelity and correcting oxidative DNA lesions (e.g., 8-oxoguanine mispairs), Msh2 directly counteracts the accumulation of somatic mutations that drive aging-associated pathologies. This places Msh2 squarely within the genomic instability hallmark of aging as a pro-longevity factor.",
"confidence": 0.92,
"key_pathways": [
"DNA mismatch repair (MMR)",
"MutSα/MutLα signaling cascade",
"oxidized purine damage recognition"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Msh2 in Mus musculus with high confidence (0.92). The mechanistic reasoning is accurate and detailed: Msh2 is indeed a core MMR component, its loss leads to microsatellite instability, accelerated tumorigenesis, and shortened lifespan in mice. The model correctly identifies the genomic instability hallmark of aging as the relevant mechanism, and accurately describes the MutSα/MutSβ heterodimer formation, MutLα recruitment, and oxidized purine recognition. All key pathways cited are correct and relevant.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}