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Gene Section
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MSH3 (mutS homolog 3 (E. coli))
Enric Domingo, Simó Schwartz Jr
Molecular Oncology and Aging Group, Molecular Biology and Biochemistry Research Center (CIBBIM),
Valle Hebron Hospital Research Institute, Barcelona, Spain
Published in Atlas Database: July 2006
Online updated version: http://AtlasGeneticsOncology.org/Genes/MSH3ID341ch5q11.html
DOI: 10.4267/2042/38352
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2006 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
associates with the MutL complex and recruits the
proteins needed for DNA excision and repair.
Hugo: MSH3
Other names: DUP; hMSH3; MRP1
Location: 5q11-q12
Local order: Between the DHFR and RASGRF2
genes.
Homology
DNA/RNA
Mutations
Description
Somatic
The MSH3 gene is composed of 24 exons spanning in a
region of 222 Kb.
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.
MSH3 is homologue to the bacterial MutS gene and to
the Msh3 gene in S. cerevisiae. Homology is higher in
the C-terminal region.
Transcription
There are two major transcripts of 5 kb and 3,8 kb
under the control of two different polyadenilation sites.
Implicated in
Protein
MSI (MicroSatellite Instability)
Description
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.
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%.
Function
Hematological malignancies
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
Oncogenesis
It has been reported loss of expression of MSH3 at the
mRNA level in some hematological malignancies
Amino acids: 1137. Molecular Weight: 127 KDa.
MSH3 is a protein involved in the mismatch repair
process after DNA replication.
Expression
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4)
251
MSH3 (mutS homolog 3 (E. coli))
Domingo E, Schwartz S Jr
Watanabe A, Ikejima M, Suzuki N, Shimada T. Genomic
organization and expression of the human MSH3 gene.
Genomics 1996;31:311-318.
including chronic myelogenous leukemia and acute
myelogenous leukemia, acute lymphocytic leukemia
and myelodysplastic syndrome.
de Wind N, Dekker M, Claij N, Jansen L, van Klink Y, Radman
M, Riggins G, van der Valk M, van't Wout K, te Riele H.
HNPCC-like cancer predisposition in mice through
simultaneous loss of Msh3 and Msh6 mismatch-repair protein
functions. Nature Genet 1999;23:359-362.
References
Fujii H, Shimada T. Isolation and characterization of cDNA
clones derived from the divergently transcribed gene in the
region upstream from the human dihydrofolate reductase gene.
J Biol Chem 1989;264:10057-10064.
Duval A, Hamelin R. Mutations at coding repeat sequences in
mismatch repair-deficient human cancers: toward a new
concept of target genes for instability. Cancer Res
2002;62:2447-2454. (Review).
Inokuchi K, Ikejima M, Watanabe A, Nakajima E, Orimo H,
Nomura T, Shimada T. Loss of expression of the human MSH3
gene in hematological malignancies. Biophys Res Commun
1995;214:171-179.
Jacob S, Praz F. DNA mismatch repair defects: role in
colorectal carcinogenesis. Biochimie 2002;84:27-47. (Review).
Risinger JI, Umar A, Boyd J, Berchuck A, Kunkel TA, Barrett
JC. Mutation of MSH3 in endometrial cancer and evidence for
its functional role in heteroduplex repair. Nature Genet
1996;14:102-109.
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4)
This article should be referenced as such:
Domingo E, Schwartz S Jr. MSH3 (mutS homolog 3 (E. coli)).
Atlas Genet Cytogenet Oncol Haematol.2006;10(4):251-252.
252