mutS

Summary

Gene Symbol: mutS
Description: methyl-directed mismatch repair protein
Alias: ECK2728, JW2703, ant, fdv, plm
Species: Escherichia coli str. K-12 substr. MG1655
Products:     mutS

Top Publications

  1. Han A, Shibata T, Takarada T, Maeda M. Gene mutation assay using a MutS protein-modified electrode. Nucleic Acids Res Suppl. 2002;:287-8 pubmed
    A novel electrochemical biosensor for gene mutation detection was developed using a DNA mismatch recognizing protein MutS from E. coli...
  2. Li G. Mechanisms and functions of DNA mismatch repair. Cell Res. 2008;18:85-98 pubmed
    ..Escherichia coli MutS and MutL and their eukaryotic homologs, MutSalpha and MutLalpha, respectively, are key players in MMR-associated ..
  3. Rye P, Delaney J, Netirojjanakul C, Sun D, Liu J, Essigmann J. Mismatch repair proteins collaborate with methyltransferases in the repair of O(6)-methylguanine. DNA Repair (Amst). 2008;7:170-6 pubmed
    ..of MTase repair of a single O(6)mG residue in cells deficient in individual mismatch repair proteins (Dam, MutH, MutS, MutL, or Vsr)...
  4. Lamers M, Winterwerp H, Sixma T. The alternating ATPase domains of MutS control DNA mismatch repair. EMBO J. 2003;22:746-56 pubmed
    ..In Escherichia coli, the MutS enzyme recognizes mismatches and initiates repair...
  5. Au K, Welsh K, Modrich P. Initiation of methyl-directed mismatch repair. J Biol Chem. 1992;267:12142-8 pubmed
    ..1987) J. Biol. Chem. 262, 15624-15629). MutH endonuclease is activated in a reaction that requires MutS, MutL, ATP, and Mg2+ and depends upon the presence of a mismatch within the DNA...
  6. Brown E, LeClerc J, Li B, Payne W, Cebula T. Phylogenetic evidence for horizontal transfer of mutS alleles among naturally occurring Escherichia coli strains. J Bacteriol. 2001;183:1631-44 pubmed
    b>mutS mutators accelerate the bacterial mutation rate 100- to 1,000-fold and relax the barriers that normally restrict homeologous recombination...
  7. Wu T, Marinus M. Deletion mutation analysis of the mutS gene in Escherichia coli. J Biol Chem. 1999;274:5948-52 pubmed
    The MutS protein is part of the dam-directed MutHLS mismatch repair pathway in Escherichia coli. We have constructed deletion derivatives in the mutS gene, which retain the P-loop coding region for ATP binding...
  8. Kunkel T, Erie D. DNA mismatch repair. Annu Rev Biochem. 2005;74:681-710 pubmed
    ..Emphasis is on structure-function studies of MMR proteins, on how mismatches are recognized, on the process by which the newly replicated strand is identified, and on excision of the replication error. ..
  9. López de Saro F, Marinus M, Modrich P, O Donnell M. The beta sliding clamp binds to multiple sites within MutL and MutS. J Biol Chem. 2006;281:14340-9 pubmed
    The MutL and MutS proteins are the central components of the DNA repair machinery that corrects mismatches generated by DNA polymerases during synthesis...

More Information

Publications65

  1. Bai H, Lu A. Physical and functional interactions between Escherichia coli MutY glycosylase and mismatch repair protein MutS. J Bacteriol. 2007;189:902-10 pubmed
    Escherichia coli MutY and MutS increase replication fidelity by removing adenines that were misincorporated opposite 7,8-dihydro-8-oxo-deoxyguanines (8-oxoG), G, or C...
  2. Jiang Y, Marszalek P. Atomic force microscopy captures MutS tetramers initiating DNA mismatch repair. EMBO J. 2011;30:2881-93 pubmed publisher
    In spite of extensive research, the mechanism by which MutS initiates DNA mismatch repair (MMR) remains controversial. We use atomic force microscopy (AFM) to capture how MutS orchestrates the first step of E. coli MMR...
  3. Galan J, Turrientes M, Baquero M, Rodríguez Alcayna M, Martínez Amado J, Martinez J, et al. Mutation rate is reduced by increased dosage of mutL gene in Escherichia coli K-12. FEMS Microbiol Lett. 2007;275:263-9 pubmed
    ..Changes in E. coli mutation frequencies derived from the gene-copy effect of mutS, mutL, mutH, uvrD, mutT, mutY, mutM, mutA, dnaE, dnaQ, and rpoS are explored...
  4. Acharya S, Foster P, Brooks P, Fishel R. The coordinated functions of the E. coli MutS and MutL proteins in mismatch repair. Mol Cell. 2003;12:233-46 pubmed
    The Escherichia coli MutS and MutL proteins have been conserved throughout evolution, although their combined functions in mismatch repair (MMR) are poorly understood...
  5. Schofield M, Nayak S, Scott T, Du C, Hsieh P. Interaction of Escherichia coli MutS and MutL at a DNA mismatch. J Biol Chem. 2001;276:28291-9 pubmed
    b>MutS and MutL are both required to activate downstream events in DNA mismatch repair...
  6. Bjornson K, Allen D, Modrich P. Modulation of MutS ATP hydrolysis by DNA cofactors. Biochemistry. 2000;39:3176-83 pubmed
    Escherichia coli MutS protein, which is required for mismatch repair, has a slow ATPase activity that obeys Michalelis-Menten kinetics. At 37 degrees C, the steady-state turnover rate for ATP hydrolysis is 1.0 +/- 0...
  7. Natrajan G, Lamers M, Enzlin J, Winterwerp H, Perrakis A, Sixma T. Structures of Escherichia coli DNA mismatch repair enzyme MutS in complex with different mismatches: a common recognition mode for diverse substrates. Nucleic Acids Res. 2003;31:4814-21 pubmed
    We have refined a series of isomorphous crystal structures of the Escherichia coli DNA mismatch repair enzyme MutS in complex with G:T, A:A, C:A and G:G mismatches and also with a single unpaired thymidine...
  8. Thomas E, Pingoud A, Friedhoff P. An efficient method for the preparation of long heteroduplex DNA as substrate for mismatch repair by the Escherichia coli MutHLS system. Biol Chem. 2002;383:1459-62 pubmed
    ..The application of this procedure is demonstrated for the analysis of the Escherichia coli MutHLS system. ..
  9. Negishi K, Loakes D, Schaaper R. Saturation of DNA mismatch repair and error catastrophe by a base analogue in Escherichia coli. Genetics. 2002;161:1363-71 pubmed
    ..At a low dose, dP is much more mutagenic in mismatch-repair-defective mutH, mutL, and mutS strains than in a wild-type strain...
  10. Wang H, Yang Y, Schofield M, Du C, Fridman Y, Lee S, et al. DNA bending and unbending by MutS govern mismatch recognition and specificity. Proc Natl Acad Sci U S A. 2003;100:14822-7 pubmed
    ..It is initiated by the recognition of base-base mismatches and insertion/deletion loops by the family of MutS proteins...
  11. Lamers M, Georgijevic D, Lebbink J, Winterwerp H, Agianian B, de Wind N, et al. ATP increases the affinity between MutS ATPase domains. Implications for ATP hydrolysis and conformational changes. J Biol Chem. 2004;279:43879-85 pubmed
    b>MutS is the key protein of the Escherichia coli DNA mismatch repair system. It recognizes mispaired and unpaired bases and has intrinsic ATPase activity...
  12. Calmann M, Nowosielska A, Marinus M. Separation of mutation avoidance and antirecombination functions in an Escherichia coli mutS mutant. Nucleic Acids Res. 2005;33:1193-200 pubmed
    ..We show that cells with the mutSDelta800 mutation (which removes the C-terminal 53 amino acids of MutS) on a multicopy plasmid are proficient for mutation avoidance...
  13. Hoffman P, Wang H, Lawrence C, Iwai S, Hanaoka F, Hays J. Binding of MutS mismatch repair protein to DNA containing UV photoproducts, "mismatched" opposite Watson--Crick and novel nucleotides, in different DNA sequence contexts. DNA Repair (Amst). 2005;4:983-93 pubmed
    ..Selective binding of mismatched or damaged DNA by MutS-homolog proteins-bacterial MutS, eukaryotic MSH2.MSH6 (MutSalpha) and MSH2...
  14. Calmann M, Nowosielska A, Marinus M. The MutS C terminus is essential for mismatch repair activity in vivo. J Bacteriol. 2005;187:6577-9 pubmed
    An Escherichia coli K-12 strain was constructed with a chromosomal deletion (mutSdelta800) in the mutS gene that produced the removal of the C-terminal 53 amino acids which are not present in the MutS crystal structure...
  15. Mukherjee S, Law S, Feig M. Deciphering the mismatch recognition cycle in MutS and MSH2-MSH6 using normal-mode analysis. Biophys J. 2009;96:1707-20 pubmed publisher
    ..The first step in mismatch repair is the recognition of base-base mismatches and insertions/deletions by bacterial MutS or eukaryotic MSH2-MSH6...
  16. Cooper D, Lahue R, Modrich P. Methyl-directed mismatch repair is bidirectional. J Biol Chem. 1993;268:11823-9 pubmed
    ..Repair of both heteroduplex orientations requires MutH, MutL, MutS, DNA helicase II, SSB, and DNA polymerase III holoenzyme, but the two substrates differ with respect to exonuclease ..
  17. Calmann M, Evans J, Marinus M. MutS inhibits RecA-mediated strand transfer with methylated DNA substrates. Nucleic Acids Res. 2005;33:3591-7 pubmed
    ..In DNA methylated by MNNG, MMR action is the result of MutS recognition of O6-methylguanine base pairs...
  18. Lopez de Saro F, O Donnell M. Interaction of the beta sliding clamp with MutS, ligase, and DNA polymerase I. Proc Natl Acad Sci U S A. 2001;98:8376-80 pubmed
    ..Thus, beta interacts with MutS, DNA ligase, and DNA polymerase I...
  19. Blackwell L, Bjornson K, Allen D, Modrich P. Distinct MutS DNA-binding modes that are differentially modulated by ATP binding and hydrolysis. J Biol Chem. 2001;276:34339-47 pubmed
    The role of MutS ATPase in mismatch repair is controversial. To clarify further the function of this activity, we have examined adenine nucleotide effects on interactions of Escherichia coli MutS with homoduplex and heteroduplex DNAs...
  20. Miller J, Funchain P, Clendenin W, Huang T, Nguyen A, Wolff E, et al. Escherichia coli strains (ndk) lacking nucleoside diphosphate kinase are powerful mutators for base substitutions and frameshifts in mismatch-repair-deficient strains. Genetics. 2002;162:5-13 pubmed
    ..Double mutants that are ndk mutS, lacking both the NDP kinase and mismatch repair, have levels of base substitutions 15-fold higher and levels of ..
  21. Manelyte L, Urbanke C, Giron Monzon L, Friedhoff P. Structural and functional analysis of the MutS C-terminal tetramerization domain. Nucleic Acids Res. 2006;34:5270-9 pubmed
    The Escherichia coli DNA mismatch repair (MMR) protein MutS is essential for the correction of DNA replication errors...
  22. Yamaguchi M, Dao V, Modrich P. MutS and MutL activate DNA helicase II in a mismatch-dependent manner. J Biol Chem. 1998;273:9197-201 pubmed
    b>MutS, MutL, and DNA helicase II are required for the mismatch-provoked excision step that occurs during Escherichia coli methyl-directed mismatch repair...
  23. Bjornson K, Blackwell L, Sage H, Baitinger C, Allen D, Modrich P. Assembly and molecular activities of the MutS tetramer. J Biol Chem. 2003;278:34667-73 pubmed
    Analytical equilibrium ultracentrifugation indicates that Escherichia coli MutS exists as an equilibrating mixture of dimers and tetramers. The association constant for the dimer-to-tetramer transition is 2...
  24. Brown J, Brown T, Fox K. Affinity of mismatch-binding protein MutS for heteroduplexes containing different mismatches. Biochem J. 2001;354:627-33 pubmed
    We have used bandshift analysis to measure the interaction between the Escherichia coli mismatch-binding protein MutS and synthetic DNA fragments containing all possible DNA mismatches as well as an unpaired T (DeltaT)...
  25. Calmann M, Marinus M. MutS inhibits RecA-mediated strand exchange with platinated DNA substrates. Proc Natl Acad Sci U S A. 2004;101:14174-9 pubmed
    ..At low levels of adduction, addition of MutS to the reaction further decreases the rate and yield in a dose-dependent manner...
  26. Mendillo M, Putnam C, Kolodner R. Escherichia coli MutS tetramerization domain structure reveals that stable dimers but not tetramers are essential for DNA mismatch repair in vivo. J Biol Chem. 2007;282:16345-54 pubmed
    The Escherichia coli mispair-binding protein MutS forms dimers and tetramers in vitro, although the functional form in vivo is under debate...
  27. Bhagwat A, Lieb M. Cooperation and competition in mismatch repair: very short-patch repair and methyl-directed mismatch repair in Escherichia coli. Mol Microbiol. 2002;44:1421-8 pubmed
    ..VSP repair and MMR share two proteins, MutS and MutL, and although the two repair pathways are not equally dependent on these proteins, their dual use creates ..
  28. Viswanathan M, Burdett V, Baitinger C, Modrich P, Lovett S. Redundant exonuclease involvement in Escherichia coli methyl-directed mismatch repair. J Biol Chem. 2001;276:31053-8 pubmed
    ..This elevation is epistatic to deficiency for MutS, suggesting an effect via the mismatch repair pathway. Our other work (Burdett, V., Baitinger, C., Viswanathan, M...
  29. Burdett V, Baitinger C, Viswanathan M, Lovett S, Modrich P. In vivo requirement for RecJ, ExoVII, ExoI, and ExoX in methyl-directed mismatch repair. Proc Natl Acad Sci U S A. 2001;98:6765-70 pubmed
    ..phenotypes associated with 2-aminopurine exposure are effectively suppressed by null mutations in mutH, mutL, mutS, or uvrD/mutU, which encode activities that act upstream of the four exonucleases in the mechanism for the methyl-..
  30. Grilley M, Griffith J, Modrich P. Bidirectional excision in methyl-directed mismatch repair. J Biol Chem. 1993;268:11830-7 pubmed
    ..The extent of excision is therefore controlled by one or more components of the repair system. ..
  31. Lebbink J, Georgijevic D, Natrajan G, Fish A, Winterwerp H, Sixma T, et al. Dual role of MutS glutamate 38 in DNA mismatch discrimination and in the authorization of repair. EMBO J. 2006;25:409-19 pubmed
    b>MutS plays a critical role in DNA mismatch repair in Escherichia coli by binding to mismatches and initiating repair in an ATP-dependent manner...
  32. Schofield M, Hsieh P. DNA mismatch repair: molecular mechanisms and biological function. Annu Rev Microbiol. 2003;57:579-608 pubmed
    ..In addition to its role in postreplication repair, the MMR machinery serves to police homologous recombination events and acts as a barrier to genetic exchange between species. ..
  33. Mendillo M, Hargreaves V, Jamison J, Mo A, Li S, Putnam C, et al. A conserved MutS homolog connector domain interface interacts with MutL homologs. Proc Natl Acad Sci U S A. 2009;106:22223-8 pubmed publisher
    Escherichia coli MutS forms a mispair-dependent ternary complex with MutL that is essential for initiating mismatch repair (MMR) but is structurally uncharacterized, in part owing to its dynamic nature...
  34. Rayssiguier C, Thaler D, Radman M. The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature. 1989;342:396-401 pubmed
    The requirement for DNA sequence homology in generalized genetic recombination is greatly relaxed in bacterial mutL, mutS and mutH mutants deficient in mismatch repair...
  35. Rasmussen L, Samson L. The Escherichia coli MutS DNA mismatch binding protein specifically binds O(6)-methylguanine DNA lesions. Carcinogenesis. 1996;17:2085-8 pubmed
    ..Here we show that the Escherichia coli MutS DNA mismatch repair binding protein does indeed bind specifically to O6MeG DNA lesions...
  36. Feng G, Tsui H, Winkler M. Depletion of the cellular amounts of the MutS and MutH methyl-directed mismatch repair proteins in stationary-phase Escherichia coli K-12 cells. J Bacteriol. 1996;178:2388-96 pubmed
    The MutL, MutS, and MutH proteins mediate methyl-directed mismatch (MDM) repair and help to maintain chromosome stability in Escherichia coli...
  37. Welsh K, Lu A, Clark S, Modrich P. Isolation and characterization of the Escherichia coli mutH gene product. J Biol Chem. 1987;262:15624-9 pubmed
    ..These findings suggest that the mutH product functions at the strand discrimination stage of mismatch correction and that this stage of the reaction involves scission of the unmethylated DNA strand. ..
  38. Feng G, Winkler M. Single-step purifications of His6-MutH, His6-MutL and His6-MutS repair proteins of escherichia coli K-12. Biotechniques. 1995;19:956-65 pubmed
    The MutS, MutH and MutL proteins mediate methyl-directed-mismatch (MDM) repair in Escherichia coli and Salmonella typhimurium...
  39. Lamers M, Perrakis A, Enzlin J, Winterwerp H, de Wind N, Sixma T. The crystal structure of DNA mismatch repair protein MutS binding to a G x T mismatch. Nature. 2000;407:711-7 pubmed
    DNA mismatch repair ensures genomic integrity on DNA replication. Recognition of a DNA mismatch by a dimeric MutS protein initiates a cascade of reactions and results in repair of the newly synthesized strand; however, details of the ..
  40. Junop M, Yang W, Funchain P, Clendenin W, Miller J. In vitro and in vivo studies of MutS, MutL and MutH mutants: correlation of mismatch repair and DNA recombination. DNA Repair (Amst). 2003;2:387-405 pubmed
    We have used the recently determined crystal structures of Escherichia coli (E. coli) MutS, MutL and MutH to guide construction of 47 amino-acid substitutions in these proteins and analyzed their behavior in mismatch repair and ..
  41. Tsui H, Feng G, Winkler M. Negative regulation of mutS and mutH repair gene expression by the Hfq and RpoS global regulators of Escherichia coli K-12. J Bacteriol. 1997;179:7476-87 pubmed
    The MutS, MutL, and MutH proteins play major roles in several DNA repair pathways. We previously reported that the cellular amounts of MutS and MutH decreased by as much as 10-fold in stationary-phase cultures...
  42. Mansour C, Doiron K, Cupples C. Characterization of functional interactions among the Escherichia coli mismatch repair proteins using a bacterial two-hybrid assay. Mutat Res. 2001;485:331-8 pubmed
    ..b>MutS and MutL, part of the post-replication mismatch repair system, stimulate VSP repair...
  43. Lieb M, Rehmat S, Bhagwat A. Interaction of MutS and Vsr: some dominant-negative mutS mutations that disable methyladenine-directed mismatch repair are active in very-short-patch repair. J Bacteriol. 2001;183:6487-90 pubmed
    ..The products of mutS and mutL, which are required for adenine methylation-directed mismatch repair (MMR), enhance VSP repair...
  44. Lahue R, Au K, Modrich P. DNA mismatch correction in a defined system. Science. 1989;245:160-4 pubmed
    ..Escherichia coli methyl-directed reaction has been reconstituted in a purified system consisting of MutH, MutL, and MutS proteins, DNA helicase II, single-strand DNA binding protein, DNA polymerase III holoenzyme, exonuclease I, DNA ..
  45. Su S, Modrich P. Escherichia coli mutS-encoded protein binds to mismatched DNA base pairs. Proc Natl Acad Sci U S A. 1986;83:5057-61 pubmed
    The Escherichia coli mutS gene product is involved in mismatch correction in this organism. We have purified a biologically active form of the 97,000 Mr protein to near homogeneity from an overproducing strain...
  46. Wu T, Marinus M. Dominant negative mutator mutations in the mutS gene of Escherichia coli. J Bacteriol. 1994;176:5393-400 pubmed
    The MutS protein of Escherichia coli is part of the dam-directed MutHLS mismatch repair pathway which rectifies replication errors and which prevents recombination between related sequences...
  47. Elez M, Radman M, Matic I. The frequency and structure of recombinant products is determined by the cellular level of MutL. Proc Natl Acad Sci U S A. 2007;104:8935-40 pubmed
    ..Although the MutS protein binds to base pair mismatches in heteroduplex DNA, the role of the MutL protein in preventing recombination ..
  48. Worth L, Clark S, Radman M, Modrich P. Mismatch repair proteins MutS and MutL inhibit RecA-catalyzed strand transfer between diverged DNAs. Proc Natl Acad Sci U S A. 1994;91:3238-41 pubmed
    Bacterial mutS and mutL mutations confer large increases in recombination between sequences that are divergent by several percent at the nucleotide level, an effect attributed to a role for products of these genes in control of ..
  49. Robertson A, Pattishall S, Gibbons E, Matson S. MutL-catalyzed ATP hydrolysis is required at a post-UvrD loading step in methyl-directed mismatch repair. J Biol Chem. 2006;281:19949-59 pubmed
    ..MutL interacts with and modulates the activities of MutS, MutH, UvrD, and perhaps other proteins...
  50. Fourrier L, Brooks P, Malinge J. Binding discrimination of MutS to a set of lesions and compound lesions (base damage and mismatch) reveals its potential role as a cisplatin-damaged DNA sensing protein. J Biol Chem. 2003;278:21267-75 pubmed
    ..shift competition assays and surface plasmon resonance, we have analyzed the interaction of Escherichia coli MutS protein with site-specifically modified DNA oligonucleotides containing each of the four cisplatin cross-links or a ..
  51. Imai M, Tago Y, Ihara M, Kawata M, Yamamoto K. Role of the 5' --> 3' exonuclease and Klenow fragment of Escherichia coli DNA polymerase I in base mismatch repair. Mol Genet Genomics. 2007;278:211-20 pubmed
    We have previously demonstrated that the Escherichia coli strain mutS DeltapolA had a higher rate of transition and minus frameshift mutations than mutS or DeltapolA strains...
  52. Joshi A, Rao B. MutS recognition: multiple mismatches and sequence context effects. J Biosci. 2001;26:595-606 pubmed
    Escherichia coli MutS is a versatile repair protein that specifically recognizes not only various types of mismatches but also single stranded loops of up to 4 nucleotides in length...
  53. Yang H, To K, Aguila S, Miller J. Metagenomic DNA fragments that affect Escherichia coli mutational pathways. Mol Microbiol. 2006;61:960-77 pubmed
    ..coli wild-type host. Mutational enhancer strains such as an ndk-deficient strain and a temperature sensitive mutS strain (mutS60) were used to further verify the mutator phenotype...
  54. Joshi A, Rao B. ATP hydrolysis induces expansion of MutS contacts on heteroduplex: a case for MutS treadmilling?. Biochemistry. 2002;41:3654-66 pubmed
    An unsolved problem in E. coli mismatch repair is how the MutS-MutL complex communicates positional information of a mismatch to MutH...
  55. Lopez Crapez E, Malinge J, Gatchitch F, Casano L, Langlois T, Pugniere M, et al. A homogeneous resonance energy transfer-based assay to monitor MutS/DNA interactions. Anal Biochem. 2008;383:301-6 pubmed publisher
    Probing the interactions of the DNA mismatch repair protein MutS with altered and damaged DNA is of great interest both for the understanding of the mismatch repair system function and for the development of tools to detect mutations...
  56. Hsieh P. Molecular mechanisms of DNA mismatch repair. Mutat Res. 2001;486:71-87 pubmed
    ..Recently, three-dimensional structures of MutS, a key repair protein that recognizes mismatches, have been determined by X-ray crystallography...