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Gene Review

mutL  -  methyl-directed mismatch repair protein

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK4166, JW4128
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Disease relevance of mutL

  • The mutA locus maps very near to, but is separable from, mutL, at about 95 min on the E. coli chromosome [1].
  • Identification and characterization of the mutL and mutS gene products of Salmonella typhimurium LT2 [2].
  • All these mutations result in a hyper-recombination phenotype, but in four-factor crosses among lambda phages, a specific loss of intragenic recombination (Pam3 X Pam80) was found in mutL and mutS mutants, as would be predicted from the postulated role of mismatch correction in gene conversion and high negative interference phenomena [3].
  • The Pms2 gene has been implicated in hereditary colon cancer and is one of several mammalian homologs of the Escherichia coli mutL DNA mismatch repair gene [4].
  • The mismatch repair system (mutS, mutL and uvrD genes) in Pseudomonas aeruginosa: molecular characterization of naturally occurring mutants [5].

High impact information on mutL

  • DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects mismatches generated during DNA replication and escape proofreading [6].
  • The requirement for DNA sequence homology in generalized genetic recombination is greatly relaxed in bacterial mutL, mutS and mutH mutants deficient in mismatch repair [7].
  • DNA mismatch repair (MMR) is one of multiple replication, repair, and recombination processes that are required to maintain genomic stability in prokaryotes and eukaryotes [8].
  • DNA mismatch-repair systems exist that repair mispaired bases formed during DNA replication, genetic recombination and as a result of damage to DNA [9].
  • Third, transformation of mutD5 strains with multicopy plasmids expressing the mutH or mutL gene restores mismatch repair, even in rapidly growing cells [10].

Chemical compound and disease context of mutL


Biological context of mutL


Anatomical context of mutL


Associations of mutL with chemical compounds

  • Such deletions are also found with starved bacteria defective in methyl-directed mismatch correction activity (mutH, mutL or mutS), and deletion mutations are also found among the much lower number of mutants that arise in bacteria wild-type for mismatch correction [19].
  • The products of mutS and mutL, which are required for adenine methylation-directed mismatch repair (MMR), enhance VSP repair [20].

Regulatory relationships of mutL

  • Mutator mutations in the mutS gene induced by the insertion of phage Mu or the transposable resistance elements Tn5 or Tn10 and those in the mutL gene induced by Tn5 or Tn10 gave mutagenic activities similar to that of the previously described mutS3 and mutL25 mutations [21].

Other interactions of mutL

  • In contrast, we found that mutations in either of two genes required for DNA-mismatch correction (mutS and mutL) selectively abolish rapid repair in the transcribed strand and render the cells moderately sensitive to UV irradiation [11].
  • Second, chromosomal miaA insertion mutations increased the spontaneous mutation frequency with a spectrum distinct from mutL mutations [22].
  • We report here the transcriptional pattern and possible posttranscriptional regulation of mutL, miaA and hfq genes of this superoperon [23].
  • Base up-regulated core genes for maltodextrin transport (lamB, mal), ATP synthase (atp), and DNA repair (recA, mutL) [24].
  • These strains contained a second unlinked mutation in either mutL or mutS or sin [25].


  1. mutA and mutC: two mutator loci in Escherichia coli that stimulate transversions. Michaels, M.L., Cruz, C., Miller, J.H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  2. Identification and characterization of the mutL and mutS gene products of Salmonella typhimurium LT2. Pang, P.P., Lundberg, A.S., Walker, G.C. J. Bacteriol. (1985) [Pubmed]
  3. Escherichia coli mutator mutants deficient in methylation-instructed DNA mismatch correction. Glickman, B.W., Radman, M. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  4. Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2. Narayanan, L., Fritzell, J.A., Baker, S.M., Liskay, R.M., Glazer, P.M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. The mismatch repair system (mutS, mutL and uvrD genes) in Pseudomonas aeruginosa: molecular characterization of naturally occurring mutants. Oliver, A., Baquero, F., Blázquez, J. Mol. Microbiol. (2002) [Pubmed]
  6. DNA mismatch repair. Kunkel, T.A., Erie, D.A. Annu. Rev. Biochem. (2005) [Pubmed]
  7. The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Rayssiguier, C., Thaler, D.S., Radman, M. Nature (1989) [Pubmed]
  8. Mammalian DNA mismatch repair. Buermeyer, A.B., Deschênes, S.M., Baker, S.M., Liskay, R.M. Annu. Rev. Genet. (1999) [Pubmed]
  9. Mismatch repair: mechanisms and relationship to cancer susceptibility. Kolodner, R.D. Trends Biochem. Sci. (1995) [Pubmed]
  10. The extreme mutator effect of Escherichia coli mutD5 results from saturation of mismatch repair by excessive DNA replication errors. Schaaper, R.M., Radman, M. EMBO J. (1989) [Pubmed]
  11. Products of DNA mismatch repair genes mutS and mutL are required for transcription-coupled nucleotide-excision repair of the lactose operon in Escherichia coli. Mellon, I., Champe, G.N. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  12. Mutagenic and comutagenic effects of ethionine in Escherichia coli K12. Zgaga, Z. Mutat. Res. (1986) [Pubmed]
  13. Differential effects of cisplatin and MNNG on dna mutants of Escherichia coli. Calmann, M.A., Marinus, M.G. Mutat. Res. (2005) [Pubmed]
  14. DNA mismatch repair and acquired cisplatin resistance in E. coli and human ovarian carcinoma cells. Massey, A., Offman, J., Macpherson, P., Karran, P. DNA Repair (Amst.) (2003) [Pubmed]
  15. The mutL repair gene of Escherichia coli K-12 forms a superoperon with a gene encoding a new cell-wall amidase. Tsui, H.C., Zhao, G., Feng, G., Leung, H.C., Winkler, M.E. Mol. Microbiol. (1994) [Pubmed]
  16. Structure of Escherichia coli K-12 miaA and characterization of the mutator phenotype caused by miaA insertion mutations. Connolly, D.M., Winkler, M.E. J. Bacteriol. (1991) [Pubmed]
  17. Bacterial genes mutL, mutS, and dcm participate in repair of mismatches at 5-methylcytosine sites. Lieb, M. J. Bacteriol. (1987) [Pubmed]
  18. DNA mismatch-repair in Escherichia coli counteracting the hydrolytic deamination of 5-methyl-cytosine residues. Zell, R., Fritz, H.J. EMBO J. (1987) [Pubmed]
  19. Mutation in Escherichia coli under starvation conditions: a new pathway leading to small deletions in strains defective in mismatch correction. Bridges, B.A., Timms, A.R. EMBO J. (1997) [Pubmed]
  20. Interaction of MutS and Vsr: some dominant-negative mutS mutations that disable methyladenine-directed mismatch repair are active in very-short-patch repair. Lieb, M., Rehmat, S., Bhagwat, A.S. J. Bacteriol. (2001) [Pubmed]
  21. Mutator mutations in Escherichia coli induced by the insertion of phage mu and the transposable resistance elements Tn5 and Tn10. Siegel, E.C., Wain, S.L., Meltzer, S.F., Binion, M.L., Steinberg, J.L. Mutat. Res. (1982) [Pubmed]
  22. Genetic and physiological relationships among the miaA gene, 2-methylthio-N6-(delta 2-isopentenyl)-adenosine tRNA modification, and spontaneous mutagenesis in Escherichia coli K-12. Connolly, D.M., Winkler, M.E. J. Bacteriol. (1989) [Pubmed]
  23. Transcriptional patterns of the mutL-miaA superoperon of Escherichia coli K-12 suggest a model for posttranscriptional regulation. Tsui, H.C., Winkler, M.E. Biochimie (1994) [Pubmed]
  24. Oxygen limitation modulates pH regulation of catabolism and hydrogenases, multidrug transporters, and envelope composition in Escherichia coli K-12. Hayes, E.T., Wilks, J.C., Sanfilippo, P., Yohannes, E., Tate, D.P., Jones, B.D., Radmacher, M.D., BonDurant, S.S., Slonczewski, J.L. BMC Microbiol. (2006) [Pubmed]
  25. Isolation and characterization of Dam+ revertants and suppressor mutations that modify secondary phenotypes of dam-3 strains of Escherichia coli K-12. McGraw, B.R., Marinus, M.G. Mol. Gen. Genet. (1980) [Pubmed]
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