Msh6 — Muts Homolog 6 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Full Name | MutS Homolog 6 |
|---|---|
| Synonyms | MSH6, mutS homolog 6, GTRAP |
| Chromosome | 2p16.3 |
| NCBI Gene ID | 4433 |
| OMIM | 604928 |
| Ensembl ID | ENSG00000182162 |
| UniProt ID | P53271 |
| Protein | [MSH6 Protein](/proteins/msh6-protein) |
| Associated Diseases | Lynch Syndrome, Alzheimer's Disease, Parkinson's Disease, ALS |
MSH6 (MutS Homolog 6) is a DNA mismatch repair (MMR) protein that partners with MSH2 to form the MutSα complex, which initiates the repair of base-base mismatches and small insertion/deletion loops. MSH6 plays a crucial role in maintaining genomic integrity in proliferating and post-mitotic cells, including neurons. Mutations in MSH6 cause Lynch syndrome (hereditary nonpolyposis colorectal cancer), and altered MSH6 expression has been implicated in the DNA repair deficits observed in neurodegenerative diseases.
MSH6 forms a heterodimer with MSH2 (MutSα):
MSH6 and DNA repair in AD:
MSH6 partners with MSH2 to form the MutSα complex, which initiates mismatch repair by recognizing base-base mismatches and small insertion/deletion loops. MSH6 contains a PCNA-interacting peptide (PIP) motif that tethers the complex to replicating DNA, ensuring repair occurs on the newly synthesized strand.
MSH6 expression is tightly regulated:
| Model | Phenotype | Key Findings |
|---|---|---|
| Msh6 knockout mice | Viable with tumors | Cancer predisposition model |
| Conditional knockout | Tissue-specific | Gastrointestinal cancers |
| Msh6 knock-in | Variable | Missense variants studied |
The study of Msh6 — Muts Homolog 6 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
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