MSH2/YOL090W Summary Help

Standard Name MSH2
Systematic Name YOL090W
Alias PMS5
Feature Type ORF, Verified
Description Protein that binds to DNA mismatches; forms heterodimers with Msh3p and Msh6p that bind to DNA mismatches to initiate the mismatch repair process; contains a Walker ATP-binding motif required for repair activity and involved in interstrand cross-link repair; Msh2p-Msh6p binds to and hydrolyzes ATP (1, 2, 3 and see Summary Paragraph)
Name Description MutS Homolog
Chromosomal Location
ChrXV:147382 to 150276 | ORF Map | GBrowse
Gbrowse
Genetic position: -83.8 cM
Gene Ontology Annotations All MSH2 GO evidence and references
  View Computational GO annotations for MSH2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 1 genes
Resources
Classical genetics
null
reduction of function
Large-scale survey
null
overexpression
Resources
305 total interaction(s) for 138 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 36
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 11
  • Biochemical Activity: 1
  • Co-fractionation: 5
  • Co-purification: 13
  • PCA: 4
  • Reconstituted Complex: 30
  • Two-hybrid: 21

Genetic Interactions
  • Dosage Rescue: 4
  • Negative Genetic: 82
  • Phenotypic Enhancement: 59
  • Phenotypic Suppression: 8
  • Positive Genetic: 10
  • Synthetic Growth Defect: 12
  • Synthetic Lethality: 6
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 964
Molecular Weight (Da) 108,883
Isoelectric Point (pI) 6.02
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:147382 to 150276 | ORF Map | GBrowse
SGD ORF map
Genetic position: -83.8 cM
Last Update Coordinates: 2006-01-05 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2895 147382..150276 2006-01-05 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005450
SUMMARY PARAGRAPH for MSH2

MSH2, MSH3, and MSH6 function in the mismatch repair (MMR) system which plays an important role in maintaining normal mutation rates (4, 5). MSH2 and MSH3 also function differentially to inhibit genetic recombination between homeologous (divergent) DNA sequences (6). In strains deficient for MSH2 and MSH3, homeologous recombination rates between repeated elements are elevated due to the loss of this inhibition (6). Msh2p interacts with Msh6p to repair G-T mismatches and insertion/deletion mismatches (7), but the binding affinity for the latter decreases as the size of the extrahelical loop increases (8). Msh2p-Msh6p interacts asymmetrically with the DNA through base-specific stacking and hydrogen-bonding interactions as well as backbone contacts (9). The Msh2p-Msh6p complex also functions in the resolution of recombination intermediates, and binds to Holliday junctions with an affinity at least as high as it has for mispaired bases (10). Disruption of MSH2 results in increased GT tract instability, and conversion of the proline residue at position 640 in Msh2p to leucine results in complete loss of protein function (11).

Msh2p is one of 6 E. coli MutS homologs in S. cerevisiae (12, 13) and a homolog of the human MSH2 protein implicated in hereditary non-polyposis colorectal cancer (HNPCC) (OMIM) (14, 15). Mutations in the S. cerevisiae Msh2p that are analagous to mutations in the human MSH2, specifically the conversion of the proline residue at position 640 to leucine, result in a defect in mismatch repair and an increase in GT tract instability (11, 16).

Last updated: 2006-09-05 Contact SGD

References cited on this page View Complete Literature Guide for MSH2
1) Antony E and Hingorani MM  (2003) Mismatch recognition-coupled stabilization of Msh2-Msh6 in an ATP-bound state at the initiation of DNA repair. Biochemistry 42(25):7682-93
2) Kijas AW, et al.  (2003) Msh2 separation of function mutations confer defects in the initiation steps of mismatch repair. J Mol Biol 331(1):123-38
3) Ward TA, et al.  (2012) Components of a fanconi-like pathway control pso2-independent DNA interstrand crosslink repair in yeast. PLoS Genet 8(8):e1002884
4) Pochart P, et al.  (1997) Conserved properties between functionally distinct MutS homologs in yeast. J Biol Chem 272(48):30345-9
5) Earley MC and Crouse GF  (1998) The role of mismatch repair in the prevention of base pair mutations in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 95(26):15487-91
6) Selva EM, et al.  (1997) Differential effects of the mismatch repair genes MSH2 and MSH3 on homeologous recombination in Saccharomyces cerevisiae. Mol Gen Genet 257(1):71-82
7) Bowers J, et al.  (1999) A mutation in the MSH6 subunit of the Saccharomyces cerevisiae MSH2-MSH6 complex disrupts mismatch recognition. J Biol Chem 274(23):16115-25
8) Habraken Y, et al.  (1998) ATP-dependent assembly of a ternary complex consisting of a DNA mismatch and the yeast MSH2-MSH6 and MLH1-PMS1 protein complexes. J Biol Chem 273(16):9837-41
9) Drotschmann K, et al.  (2001) Asymmetric recognition of DNA local distortion. Structure-based functional studies of eukaryotic Msh2-Msh6. J Biol Chem 276(49):46225-9
10) Marsischky GT, et al.  (1999) 'Saccharomyces cerevisiae MSH2/6 complex interacts with Holliday junctions and facilitates their cleavage by phage resolution enzymes. J Biol Chem 274(11):7200-6
11) Polaczek P, et al.  (1998) Functional genetic tests of DNA mismatch repair protein activity in Saccharomyces cerevisiae. Gene 213(1-2):159-67
12) Fishel R, et al.  (1993) The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75(5):1027-38
13) Harfe BD and Jinks-Robertson S  (2000) Mismatch repair proteins and mitotic genome stability. Mutat Res 451(1-2):151-67
14) Leach FS, et al.  (1993) Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75(6):1215-25
15) Reenan RA and Kolodner RD  (1992) Isolation and characterization of two Saccharomyces cerevisiae genes encoding homologs of the bacterial HexA and MutS mismatch repair proteins. Genetics 132(4):963-73
16) Studamire B, et al.  (1999) Separation-of-function mutations in Saccharomyces cerevisiae MSH2 that confer mismatch repair defects but do not affect nonhomologous-tail removal during recombination. Mol Cell Biol 19(11):7558-67