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Msh2p

Msh2p (Saccharomyces cerevisiae) is product of expression of MSH2 gene.


Msh2p is involved in:

MMR in Saccharomyces cerevisiae

Keywords:



FUNCTION: Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2- MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer), which bind to DNA mismatches thereby initiating DNA repair. MSH2 seems to act as a scaffold for the other MutS homologs that provide substrate-binding and substrate-specificity. When bound, heterodimers bend the DNA helix and shield approximately 20 base pairs. MutS alpha acts mainly to repair base-base and single insertion-deletion mismatches that occur during replication, but can also repair longer insertion-deletion loops (IDLs), although with decreasing efficiency as the size of the extrahelical loop increases. MutS beta acts mainly to repair IDLs from 2 to 13 nucleotides in size, but can also repair base-base and single insertion-deletion mismatches. After mismatch binding, MutS alpha or beta form a ternary complex with a MutL heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. Both subunits bind ATP, but with differing affinities, and their ATPase kinetics are also very different. MSH6 binds and hydrolyzes ATP rapidly, whereas MSH2 catalyzes ATP at a substantially slower rate. Binding to a mismatched base pair suppresses MSH6-catalyzed ATP hydrolysis, but not the activity of MSH2. ATP binding to both subunits is necessary to trigger a change in MutS alpha interaction with mismatched DNA, converting MutS alpha into a sliding clamp capable of hydrolysis-independent movement along DNA, and also facilitates formation of ternary complexes containing MutS and MutL proteins and the mismatch. MutS beta also has a role in regulation of heteroduplex formation during mitotic and meiotic recombination. MutS beta binds to DNA flap structures predicted to form during recombination, and is required for 3' non-homologous tail removal (NHTR). MutS beta- binding alters the DNA conformation of its substrate at the ds/ssDNA junction and may facilitate its recognition and/or cleavage by the downstream nucleotide excision repair (NER) RAD1- RAD10 endonuclease.

ENZYME REGULATION: Inhibited by Cd(2+).

SUBUNIT: Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2- MSH3 (MutS beta). Both heterodimers form a ternary complex with MutL alpha (MLH1-PMS1). MutS beta also forms a ternary complex with MutL beta (MLH1-MLH3), and possibly with a MLH1-MLH2 heterodimer. Both heterodimers interact with proliferating cell nuclear antigen (PCNA/POL30). This interaction is disrupted upon binding of the MutS heterodimers to mismatch DNA. Interacts with SAW1.

INTERACTION: P39875:EXO1; NbExp=3; IntAct=EBI-11352, EBI-6738; Q03834:MSH6; NbExp=2; IntAct=EBI-11352, EBI-11383; Q05471:SWR1; NbExp=1; IntAct=EBI-11352, EBI-22102; P53257:TPC1; NbExp=1; IntAct=EBI-11352, EBI-2095999;

SUBCELLULAR LOCATION: Nucleus.

MISCELLANEOUS: Present with 1230 molecules/cell in log phase SD medium.

SIMILARITY: Belongs to the DNA mismatch repair mutS family.


NCBI GenPept GI number(s): 6324482
Species: Saccharomyces cerevisiae

Links to other databases:

Database ID Link
Uniprot P25847 P25847
PFAM: - P25847 (Link - using uniprot id)
InterPro: - P25847 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MSSTRPELKFSDVSEERNFYKKYTGLPKKPLKTIRLVDKGDYYTVIGSDA
IFVADSVYHTQSVLKNCQLDPVTAKNFHEPTKYVTVSLQVLATLLKLCLL
DLGYKVEIYDKGWKLIKSASPGNIEQVNELMNMNIDSSIIIASLKVQWNS
QDGNCIIGVAFIDTTAYKVGMLDIVDNEVYSNLESFLIQLGVKECLVQDL
TSNSNSNAEMQKVINVIDRCGCVVTLLKNSEFSEKDVELDLTKLLGDDLA
LSLPQKYSKLSMGACNALIGYLQLLSEQDQVGKYELVEHKLKEFMKLDAS
AIKALNLFPQGPQNPFGSNNLAVSGFTSAGNSGKVTSLFQLLNHCKTNAG
VRLLNEWLKQPLTNIDEINKRHDLVDYLIDQIELRQMLTSEYLPMIPDIR
RLTKKLNKRGNLEDVLKIYQFSKRIPEIVQVFTSFLEDDSPTEPVNELVR
SVWLAPLSHHVEPLSKFEEMVETTVDLDAYEENNEFMIKVEFNEELGKIR
SKLDTLRDEIHSIHLDSAEDLGFDPDKKLKLENHHLHGWCMRLTRNDAKE
LRKHKKYIELSTVKAGIFFSTKQLKSIANETNILQKEYDKQQSALVREII
NITLTYTPVFEKLSLVLAHLDVIASFAHTSSYAPIPYIRPKLHPMDSERR
THLISSRHPVLEMQDDISFISNDVTLESGKGDFLIITGPNMGGKSTYIRQ
VGVISLMAQIGCFVPCEEAEIAIVDAILCRVGAGDSQLKGVSTFMVEILE
TASILKNASKNSLIIVDELGRGTSTYDGFGLAWAIAEHIASKIGCFALFA
THFHELTELSEKLPNVKNMHVVAHIEKNLKEQKHDDEDITLLYKVEPGIS
DQSFGIHVAEVVQFPEKIVKMAKRKANELDDLKTNNEDLKKAKLSLQEVN
EGNIRLKALLKEWIRKVKEEGLHDPSKITEEASQHKIQELLRAIANEPEK
ENDNYLKYIKALLL

Msh2p (Saccharomyces cerevisiae) is able to recognize following damages:
Msh2p (Saccharomyces cerevisiae) belongs to following protein families:
References:

Title Authors Journal
Isolation and characterization of two Saccharomyces cerevisiae genes encoding homologs of the bacterial HexA and MutS mismatch repair proteins. Reenan RA, Kolodner RD Genetics Dec. 1, 1992
Characterization of insertion mutations in the Saccharomyces cerevisiae MSH1 and MSH2 genes: evidence for separate mitochondrial and nuclear functions. Reenan RA, Kolodner RD Genetics Dec. 1, 1992
MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast. Prolla TA, Pang Q, Alani E, Kolodner RD, Liskay RM Science Aug. 19, 1994
A 29.425 kb segment on the left arm of yeast chromosome XV contains more than twice as many unknown as known open reading frames. Zumstein E, Pearson BM, Kalogeropoulos A, Schweizer M Yeast Aug. 1, 1995
Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Marsischky GT, Filosi N, Kane MF, Kolodner R Genes Dev Jan. 15, 1996
Binding of insertion/deletion DNA mismatches by the heterodimer of yeast mismatch repair proteins MSH2 and MSH3. Habraken Y, Sung P, Prakash L, Prakash S Curr Biol Sept. 1, 1996
The Saccharomyces cerevisiae Msh2 and Msh6 proteins form a complex that specifically binds to duplex oligonucleotides containing mismatched DNA base pairs. Alani E Mol Cell Biol Oct. 1, 1996
Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Umar A, Buermeyer AB, Simon JA, Thomas DC, Clark AB, Liskay RM, Kunkel TA Cell Oct. 4, 1996
The nucleotide sequence of Saccharomyces cerevisiae chromosome XV. Dujon B, Albermann K, Aldea M, Alexandraki D, Ansorge W, Arino J, Benes V, Bohn C, Bolotin-Fukuhara M, Bordonne R, Boyer J, Camasses A, Casamayor A, Casas C, Cheret G, Cziepluch C, Daignan-Fornier B, Dang DV, de Haan M, Delius H, Durand P, Fairhead C, Feldmann H, Gaillon L, Kleine K, et al. Nature May 1, 1997
Microsatellite instability in yeast: dependence on repeat unit size and DNA mismatch repair genes. Sia EA, Kokoska RJ, Dominska M, Greenwell P, Petes TD Mol Cell Biol May 1, 1997
Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in double-strand break-induced recombination. Sugawara N, Paques F, Colaiacovo M, Haber JE Proc Natl Acad Sci U S A Aug. 19, 1997
Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-PMS1 complex. Habraken Y, Sung P, Prakash L, Prakash S Curr Biol Oct. 1, 1997
ATP-dependent assembly of a ternary complex consisting of a DNA mismatch and the yeast MSH2-MSH6 and MLH1-PMS1 protein complexes. Habraken Y, Sung P, Prakash L, Prakash S J Biol Chem April 17, 1998
The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations. Flores-Rozas H, Kolodner RD Proc Natl Acad Sci U S A Oct. 13, 1998
Saccharomyces cerevisiae Msh2p and Msh6p ATPase activities are both required during mismatch repair. Studamire B, Quach T, Alani E Mol Cell Biol Dec. 1, 1998
'Saccharomyces cerevisiae MSH2/6 complex interacts with Holliday junctions and facilitates their cleavage by phage resolution enzymes. Marsischky GT, Lee S, Griffith J, Kolodner RD J Biol Chem March 12, 1999
Mutator phenotypes of yeast strains heterozygous for mutations in the MSH2 gene. Drotschmann K, Clark AB, Tran HT, Resnick MA, Gordenin DA, Kunkel TA Proc Natl Acad Sci U S A March 16, 1999
Mutator phenotypes of common polymorphisms and missense mutations in MSH2. Drotschmann K, Clark AB, Kunkel TA Curr Biol Aug. 26, 1999
MSH2 and MSH6 are required for removal of adenine misincorporated opposite 8-oxo-guanine in S. cerevisiae. Ni TT, Marsischky GT, Kolodner RD Mol Cell Sept. 1, 1999
Biochemical characterization of the interaction between the Saccharomyces cerevisiae MSH2-MSH6 complex and mispaired bases in DNA. Marsischky GT, Kolodner RD J Biol Chem Sept. 17, 1999
Separation-of-function mutations in Saccharomyces cerevisiae MSH2 that confer mismatch repair defects but do not affect nonhomologous-tail removal during recombination. Studamire B, Price G, Sugawara N, Haber JE, Alani E Mol Cell Biol Nov. 1, 1999
Functional interaction of proliferating cell nuclear antigen with MSH2-MSH6 and MSH2-MSH3 complexes. Clark AB, Valle F, Drotschmann K, Gary RK, Kunkel TA J Biol Chem Nov. 24, 2000
MSH-MLH complexes formed at a DNA mismatch are disrupted by the PCNA sliding clamp. Bowers J, Tran PT, Joshi A, Liskay RM, Alani E J Mol Biol March 9, 2001
Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae. Ellison AR, Lofing J, Bitter GA Hum Mol Genet Sept. 1, 2001
Asymmetric recognition of DNA local distortion. Structure-based functional studies of eukaryotic Msh2-Msh6. Drotschmann K, Yang W, Brownewell FE, Kool ET, Kunkel TA J Biol Chem Dec. 7, 2001
Evidence for sequential action of two ATPase active sites in yeast Msh2-Msh6. Drotschmann K, Yang W, Kunkel TA DNA Repair (Amst) Sept. 4, 2002
Transfer of the MSH2.MSH6 complex from proliferating cell nuclear antigen to mispaired bases in DNA. Lau PJ, Kolodner RD J Biol Chem Feb. 3, 2003
Mismatch recognition-coupled stabilization of Msh2-Msh6 in an ATP-bound state at the initiation of DNA repair. Antony E, Hingorani MM Biochemistry July 1, 2003
Msh2 separation of function mutations confer defects in the initiation steps of mismatch repair. Kijas AW, Studamire B, Alani E J Mol Biol Aug. 1, 2003
Global analysis of protein expression in yeast. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK, Weissman JS Nature Oct. 16, 2003
Global analysis of protein localization in budding yeast. Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, O'Shea EK Nature Oct. 16, 2003
Cadmium inhibits the functions of eukaryotic MutS complexes. Clark AB, Kunkel TA J Biol Chem Dec. 24, 2004
Cadmium inhibits mismatch repair by blocking the ATPase activity of the MSH2-MSH6 complex. Banerjee S, Flores-Rozas H Nucleic Acids Res Jan. 1, 2005
Analysis of the interaction between the Saccharomyces cerevisiae MSH2-MSH6 and MLH1-PMS1 complexes with DNA using a reversible DNA end-blocking system. Mendillo ML, Mazur DJ, Kolodner RD J Biol Chem June 10, 2005
Detection of high-affinity and sliding clamp modes for MSH2-MSH6 by single-molecule unzipping force analysis. Jiang J, Bai L, Surtees JA, Gemici Z, Wang MD, Alani E Mol Cell Dec. 9, 2005
Contribution of Msh2 and Msh6 subunits to the asymmetric ATPase and DNA mismatch binding activities of Saccharomyces cerevisiae Msh2-Msh6 mismatch repair protein. Antony E, Khubchandani S, Chen S, Hingorani MM DNA Repair (Amst) Jan. 3, 2006
Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-Msh6(ATP) state capable of hydrolysis-independent movement along DNA. Mazur DJ, Mendillo ML, Kolodner RD Mol Cell April 7, 2006
Analysis of the proteins involved in the in vivo repair of base-base mismatches and four-base loops formed during meiotic recombination in the yeast Saccharomyces cerevisiae. Stone JE, Petes TD Genetics July 1, 2006
Mismatch repair factor MSH2-MSH3 binds and alters the conformation of branched DNA structures predicted to form during genetic recombination. Surtees JA, Alani E J Mol Biol July 14, 2006
Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display distinct requirements for DNA binding domain I in mismatch recognition. Lee SD, Surtees JA, Alani E J Mol Biol Jan. 9, 2007
Saccharomyces cerevisiae Msh2-Msh3 acts in repair of base-base mispairs. Harrington JM, Kolodner RD Mol Cell Biol Sept. 1, 2007
Microarray-based genetic screen defines SAW1, a gene required for Rad1/Rad10-dependent processing of recombination intermediates. Li F, Dong J, Pan X, Oum JH, Boeke JD, Lee SE Mol Cell May 9, 2008


Last modification of this entry: Oct. 13, 2010.

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