MSH6/YDR097C Summary Help

Standard Name MSH6
Systematic Name YDR097C
Alias PMS3 , PMS6 1
Feature Type ORF, Verified
Description Protein required for mismatch repair in mitosis and meiosis; forms a complex with Msh2p to repair both single-base & insertion-deletion mispairs; also involved in interstrand cross-link repair; potentially phosphorylated by Cdc28p (2, 3, 4, 5 and see Summary Paragraph)
Name Description MutS Homolog
Chromosomal Location
ChrIV:643837 to 640109 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All MSH6 GO evidence and references
  View Computational GO annotations for MSH6
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 2 genes
Resources
Classical genetics
null
Large-scale survey
null
overexpression
Resources
155 total interaction(s) for 61 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 51
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 2
  • Biochemical Activity: 2
  • Co-fractionation: 5
  • Co-purification: 7
  • Reconstituted Complex: 17
  • Two-hybrid: 4

Genetic Interactions
  • Dosage Growth Defect: 3
  • Dosage Lethality: 1
  • Dosage Rescue: 5
  • Negative Genetic: 8
  • Phenotypic Enhancement: 33
  • Phenotypic Suppression: 3
  • Positive Genetic: 2
  • Synthetic Growth Defect: 3
  • Synthetic Lethality: 8

Resources
Expression Summary
histogram
Resources
Length (a.a.) 1,242
Molecular Weight (Da) 140,079
Isoelectric Point (pI) 5.63
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:643837 to 640109 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..3729 643837..640109 2011-02-03 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 SGDIDS000002504
SUMMARY PARAGRAPH for MSH6

MSH6, MSH2, and MSH3 function in the mismatch repair (MMR) system which plays an important role in substantially lowering mutation rates and blocking recombination between nonidentical sequences (2,6, 7). Msh6p interacts with Msh2p to repair GT mismatches and insertion/deletion mismatches (2,3), 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). The Msh6p subunit of the Msh2p-Msh6p complex appears to use its ATP binding or hydrolysis activity to coordinate mismatch binding with additional mismatch repair components such as the Mlh1p-Pms1p complex, leading to the formation of a ternary complex (11, 8). Msh6p and Msh3p also function in removing specific types of frameshift intermediates (12). Mutations in MSH6 or MSH3 cause partial defects in MMR, with inactivation of MSH6 resulting in high rates of base-substitution mutations and low rates of frameshift mutations (1).

Msh6p is one of 6 E. coli MutS homologs in S. cerevisiae (13). Mutations in the human MSH6 protein have been identified in an endometrial carcinoma cell line (14).

Last updated: 2002-10-28 Contact SGD

References cited on this page View Complete Literature Guide for MSH6
1) Das Gupta R and Kolodner RD  (2000) Novel dominant mutations in Saccharomyces cerevisiae MSH6. Nat Genet 24(1):53-6
2) Marsischky GT, et al.  (1996) Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dev 10(4):407-20
3) 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
4) Ubersax JA, et al.  (2003) Targets of the cyclin-dependent kinase Cdk1. Nature 425(6960):859-64
5) 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
6) Pochart P, et al.  (1997) Conserved properties between functionally distinct MutS homologs in yeast. J Biol Chem 272(48):30345-9
7) 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
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) Studamire B, et al.  (1998) Saccharomyces cerevisiae Msh2p and Msh6p ATPase activities are both required during mismatch repair. Mol Cell Biol 18(12):7590-601
12) Harfe BD and Jinks-Robertson S  (1999) Removal of frameshift intermediates by mismatch repair proteins in Saccharomyces cerevisiae. Mol Cell Biol 19(7):4766-73
13) Harfe BD and Jinks-Robertson S  (2000) Mismatch repair proteins and mitotic genome stability. Mutat Res 451(1-2):151-67
14) Risinger JI, et al.  (1996) Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair. Nat Genet 14(1):102-5