MSH3 mutS homolog 3 (E. coli)
2006-07-01 Enric Domingo , Simo Schwartz Jr AffiliationOncologia Molecular i Envelliment, Centre dInvestigacions en Bioqumica i Biologia Molecular (CIBBIM) Hospital Universitari Vall dHebron Passeig Vall dHebron 119-129 Barcelona 08035, Catalonia, Spain
DNA/RNA
Description
The MSH3 gene is composed of 24 exons spanning in a region of 222 Kb.
Transcription
There are two major transcripts of 5 kb and 3,8 kb under the control of two different polyadenilation sites.
Proteins
Description
Amino acids: 1137. Molecular Weight: 127 KDa. MSH3 is a protein involved in the mismatch repair process after DNA replication.
Expression
Expression of MSH3 together with the dihydrofolate reductase (DHFR) gene appear to be regulated by a bidirectional promoter composed of multiple GC boxes and two initiator elements. MSH3 is expressed in all human tissues at low levels but with variable intensities, with higher expression in testis and pancreas and lower in small intestine and colon.
Function
MSH3 binds to MSH2 to form the MutSb heterodimer, which binds to insertion-deletion mismatches of two or more base pairs. Thereafter the MutS complex associates with the MutL complex and recruits the proteins needed for DNA excision and repair.
Homology
MSH3 is homologue to the bacterial MutS gene and to the Msh3 gene in S. cerevisiae. Homology is higher in the C-terminal region.
Mutations
Somatic
MSH3 has insertions/deletions in a A(8) repeat in tumours showing microsatellite instability (MSI). As MSH3 is a mismatch repair gene and is mutated in a microsatellite only in MSI tumours is considered to be a secondary mutator that enhances a more severe MSI.
Implicated in
Entity name
MSI (MicroSatellite Instability).
Note
Tumours in which the molecular feature that leads to cancer is the lost of the mismatch repair (MMR) system.
Disease
This phenotype is present in 15% of colorectal cancer, gastric cancer and endometrial cancer, and with lower incidence in some other tissues.
Oncogenesis
The average frequencies of the microsatellite mutation reported in sporadic MSI from colorectal, gastric and endometrial cancer are 38%, 39% and 25% respectively. In hereditary MSI (or HNPCC) is 51%.
Entity name
Hematological malignancies.
Oncogenesis
It has been reported loss of expression of MSH3 at the mRNA level in some hematological malignancies including chronic myelogenous leukemia and acute myelogenous leukemia, acute lymphocytic leukemia and myelodysplastic syndrome.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11980631 | 2002 | Mutations at coding repeat sequences in mismatch repair-deficient human cancers: toward a new concept of target genes for instability. | Duval A et al |
| 2722860 | 1989 | Isolation and characterization of cDNA clones derived from the divergently transcribed gene in the region upstream from the human dihydrofolate reductase gene. | Fujii H et al |
| 7669036 | 1995 | Loss of expression of the human MSH3 gene in hematological malignancies. | Inokuchi K et al |
| 11900875 | 2002 | DNA mismatch repair defects: role in colorectal carcinogenesis. | Jacob S et al |
| 8782829 | 1996 | Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair. | Risinger JI et al |
| 8838312 | 1996 | Genomic organization and expression of the human MSH3 gene. | Watanabe A et al |
| 10545954 | 1999 | HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions. | de Wind N et al |
Other Information
Locus ID:
NCBI: 4437
MIM: 600887
HGNC: 7326
Ensembl: ENSG00000113318
Variants:
dbSNP: 4437
ClinVar: 4437
TCGA: ENSG00000113318
COSMIC: MSH3
RNA/Proteins
Expression (GTEx)
Pathways
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA128406956 | fluorouracil | Chemical | VariantAnnotation | not associated | PD | 28796378 | |
| PA164713176 | Platinum compounds | Chemical | VariantAnnotation | not associated | PD | 28796378 | |
| PA166122986 | radiotherapy | Chemical | VariantAnnotation | not associated | PD | 28796378 | |
| PA445742 | Stomach Neoplasms | Disease | VariantAnnotation | not associated | PD | 28796378 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38281411 | 2024 | High-throughput sequencing and in-silico analysis confirm pathogenicity of novel MSH3 variants in African American colorectal cancer. | 0 |
| 38281411 | 2024 | High-throughput sequencing and in-silico analysis confirm pathogenicity of novel MSH3 variants in African American colorectal cancer. | 0 |
| 35675019 | 2023 | A large family with MSH3-related polyposis. | 3 |
| 37140056 | 2023 | MSH2-MSH3 promotes DNA end resection during homologous recombination and blocks polymerase theta-mediated end-joining through interaction with SMARCAD1 and EXO1. | 5 |
| 37402566 | 2023 | MSH3: a confirmed predisposing gene for adenomatous polyposis. | 2 |
| 37888748 | 2023 | Novel insights into the ecDNA formation mechanism involving MSH3 in methotrexate‑resistant human colorectal cancer cells. | 0 |
| 35675019 | 2023 | A large family with MSH3-related polyposis. | 3 |
| 37140056 | 2023 | MSH2-MSH3 promotes DNA end resection during homologous recombination and blocks polymerase theta-mediated end-joining through interaction with SMARCAD1 and EXO1. | 5 |
| 37402566 | 2023 | MSH3: a confirmed predisposing gene for adenomatous polyposis. | 2 |
| 37888748 | 2023 | Novel insights into the ecDNA formation mechanism involving MSH3 in methotrexate‑resistant human colorectal cancer cells. | 0 |
| 33596761 | 2021 | Coordinated roles of SLX4 and MutSβ in DNA repair and the maintenance of genome stability. | 13 |
| 34250384 | 2021 | Prevalence and Characterization of Biallelic and Monoallelic NTHL1 and MSH3 Variant Carriers From a Pan-Cancer Patient Population. | 7 |
| 33596761 | 2021 | Coordinated roles of SLX4 and MutSβ in DNA repair and the maintenance of genome stability. | 13 |
| 34250384 | 2021 | Prevalence and Characterization of Biallelic and Monoallelic NTHL1 and MSH3 Variant Carriers From a Pan-Cancer Patient Population. | 7 |
| 31549400 | 2020 | EMAST status as a beneficial predictor of fluorouracil-based adjuvant chemotherapy for Stage II/III colorectal cancer. | 3 |
Citation
Enric Domingo ; Simo Schwartz Jr
MSH3 mutS homolog 3 (E. coli)
Atlas Genet Cytogenet Oncol Haematol. 2006-07-01
Online version: http://atlasgeneticsoncology.org/gene/341/msh3-muts-homolog-3-(e-coli)
