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Target intelligence / Profile preview
DNA mismatch repair protein Mlh3 (MLH3)
- Target
- MLH3
- Molecular classification
- Enzyme (specifically, an endonuclease as part of the MutLγ complex), DNA repair protein (MutL-homolog family), Other (heterodimeric protein, forms MutLγ with MLH1)
01
Overview
DNA mismatch repair protein Mlh3 (MLH3) is a member of the MutL-homolog family of proteins essential for the repair of DNA mismatches that arise during DNA replication and recombination, thereby maintaining genomic stability[1][2][4]. It forms a heterodimer with MLH1, known as the MutLγ complex, which possesses a latent endonuclease activity involved in both the resolution of meiotic double Holliday junctions and the repair of mismatched bases[1][5][6]. Somatic or germline mutations in MLH3 are linked to microsatellite instability in tumors and hereditary nonpolyposis colorectal cancer type 7 (HNPCC7)[1][2][4]. Besides its prominent role in DNA repair, MLH3 also participates in antibody diversification and is implicated in triplet repeat expansion responsible for several human neurological disorders[3][5][6]. MLH3 dysfunction may cause genomic instability, cancer susceptibility, infertility, and altered patterns of antibody gene diversification[2][3][6].
- Other names
- DNA mismatch repair protein Mlh3MutL homolog 3MutL protein homolog 3HNPCC7
02
Mechanism of action
No direct drugs, but as an endonuclease in DNA repair, hypothetical drug mechanisms could involve inhibition or modulation of mismatch repair or modulation of meiotic recombination
03
Biological functions
DNA mismatch repair (MMR)Meiotic recombination/crossover resolutionMaintenance of genome stabilityAntibody maturation (class switch recombination and somatic hypermutation)
04
Disease associations
Cancer (notably hereditary nonpolyposis colorectal cancer type 7, HNPCC7, and microsatellite instability tumors)Neurodegenerative disease (implicated in triplet repeat expansions causing neurological disorders)
05
Safety considerations
Inhibition or mutation results in increased genomic instability and cancer riskDeficiency leads to meiotic defects (infertility, aneuploidy in model organisms)
06
Biomarkers
Microsatellite instability (MSI), especially in cancersGermline MLH3 mutations (for hereditary colon cancer risk)
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