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Nucleic Acids Res. 1998 February 15; 26(4): 948–953.
PMCID: PMC147374

The Escherichia coli MutL protein stimulates binding of Vsr and MutS to heteroduplex DNA.


Vsr DNA mismatch endonuclease is the key enzyme of very short patch (VSP) DNA mismatch repair and nicks the T-containing strand at the site of a T-G mismatch in a sequence-dependent manner. MutS is part of the mutHLS repair system and binds to diverse mismatches in DNA. The function of the mutL gene product is currently unclear but mutations in the gene abolish mutHLS -dependent repair. The absence of MutL severely reduces VSP repair but does not abolish it. Purified MutL appears to act catalytically to bind Vsr to its substrate; one-hundredth of an equivalent of MutL is sufficient to bring about a significant effect. MutL enhances binding of MutS to its substrate 6-fold but does so in a stoichiometric manner. Mutational studies indicate that the MutL interaction region lies within the N-terminal 330 amino acids and that the MutL multimerization region is at the C-terminal end. MutL mutant monomeric forms can stimulate MutS binding.

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Selected References

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  • Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994 Sep 15;54(18):4855–4878. [PubMed]
  • Hattman S. Partial purification of the Escherichia coli K-12 mec+ deoxyribonucleic acid-cytosine methylase: in vitro methylation completely protects bacteriophage lambda deoxyribonucleic acid against cleavage by R-EcoRII. J Bacteriol. 1977 Mar;129(3):1330–1334. [PMC free article] [PubMed]
  • Coulondre C, Miller JH, Farabaugh PJ, Gilbert W. Molecular basis of base substitution hotspots in Escherichia coli. Nature. 1978 Aug 24;274(5673):775–780. [PubMed]
  • Lieb M, Bhagwat AS. Very short patch repair: reducing the cost of cytosine methylation. Mol Microbiol. 1996 May;20(3):467–473. [PubMed]
  • Sohail A, Lieb M, Dar M, Bhagwat AS. A gene required for very short patch repair in Escherichia coli is adjacent to the DNA cytosine methylase gene. J Bacteriol. 1990 Aug;172(8):4214–4221. [PMC free article] [PubMed]
  • Hennecke F, Kolmar H, Bründl K, Fritz HJ. The vsr gene product of E. coli K-12 is a strand- and sequence-specific DNA mismatch endonuclease. Nature. 1991 Oct 24;353(6346):776–778. [PubMed]
  • Lieb M. Specific mismatch correction in bacteriophage lambda crosses by very short patch repair. Mol Gen Genet. 1983;191(1):118–125. [PubMed]
  • Lieb M, Allen E, Read D. Very short patch mismatch repair in phage lambda: repair sites and length of repair tracts. Genetics. 1986 Dec;114(4):1041–1060. [PubMed]
  • Gläsner W, Merkl R, Schellenberger V, Fritz HJ. Substrate preferences of Vsr DNA mismatch endonuclease and their consequences for the evolution of the Escherichia coli K-12 genome. J Mol Biol. 1995 Jan 6;245(1):1–7. [PubMed]
  • Lieb M, Rehmat S. Very short patch repair of T:G mismatches in vivo: importance of context and accessory proteins. J Bacteriol. 1995 Feb;177(3):660–666. [PMC free article] [PubMed]
  • Dzidic S, Radman M. Genetic requirements for hyper-recombination by very short patch mismatch repair: involvement of Escherichia coli DNA polymerase I. Mol Gen Genet. 1989 Jun;217(2-3):254–256. [PubMed]
  • Zell R, Fritz HJ. DNA mismatch-repair in Escherichia coli counteracting the hydrolytic deamination of 5-methyl-cytosine residues. EMBO J. 1987 Jun;6(6):1809–1815. [PubMed]
  • Lieb M. Bacterial genes mutL, mutS, and dcm participate in repair of mismatches at 5-methylcytosine sites. J Bacteriol. 1987 Nov;169(11):5241–5246. [PMC free article] [PubMed]
  • Jones M, Wagner R, Radman M. Mismatch repair of deaminated 5-methyl-cytosine. J Mol Biol. 1987 Mar 5;194(1):155–159. [PubMed]
  • Parker BO, Marinus MG. Repair of DNA heteroduplexes containing small heterologous sequences in Escherichia coli. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1730–1734. [PubMed]
  • Modrich P, Lahue R. Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu Rev Biochem. 1996;65:101–133. [PubMed]
  • Su SS, Modrich P. Escherichia coli mutS-encoded protein binds to mismatched DNA base pairs. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5057–5061. [PubMed]
  • Au KG, Welsh K, Modrich P. Initiation of methyl-directed mismatch repair. J Biol Chem. 1992 Jun 15;267(17):12142–12148. [PubMed]
  • Grilley M, Welsh KM, Su SS, Modrich P. Isolation and characterization of the Escherichia coli mutL gene product. J Biol Chem. 1989 Jan 15;264(2):1000–1004. [PubMed]
  • Allen DJ, Makhov A, Grilley M, Taylor J, Thresher R, Modrich P, Griffith JD. MutS mediates heteroduplex loop formation by a translocation mechanism. EMBO J. 1997 Jul 16;16(14):4467–4476. [PubMed]
  • Pang Q, Prolla TA, Liskay RM. Functional domains of the Saccharomyces cerevisiae Mlh1p and Pms1p DNA mismatch repair proteins and their relevance to human hereditary nonpolyposis colorectal cancer-associated mutations. Mol Cell Biol. 1997 Aug;17(8):4465–4473. [PMC free article] [PubMed]
  • Welsh KM, Lu AL, Clark S, Modrich P. Isolation and characterization of the Escherichia coli mutH gene product. J Biol Chem. 1987 Nov 15;262(32):15624–15629. [PubMed]
  • Umar A, Kunkel TA. DNA-replication fidelity, mismatch repair and genome instability in cancer cells. Eur J Biochem. 1996 Jun 1;238(2):297–307. [PubMed]
  • Merkl R, Kröger M, Rice P, Fritz HJ. Statistical evaluation and biological interpretation of non-random abundance in the E. coli K-12 genome of tetra- and pentanucleotide sequences related to VSP DNA mismatch repair. Nucleic Acids Res. 1992 Apr 11;20(7):1657–1662. [PMC free article] [PubMed]
  • Bhagwat AS, McClelland M. DNA mismatch correction by Very Short Patch repair may have altered the abundance of oligonucleotides in the E. coli genome. Nucleic Acids Res. 1992 Apr 11;20(7):1663–1668. [PMC free article] [PubMed]
  • Kulakauskas S, Barsomian JM, Lubys A, Roberts RJ, Wilson GG. Organization and sequence of the HpaII restriction-modification system and adjacent genes. Gene. 1994 May 3;142(1):9–15. [PubMed]
  • Kiss A, Posfai G, Keller CC, Venetianer P, Roberts RJ. Nucleotide sequence of the BsuRI restriction-modification system. Nucleic Acids Res. 1985 Sep 25;13(18):6403–6421. [PMC free article] [PubMed]
  • Zhang B, Tao T, Wilson GG, Blumenthal RM. The M.AluI DNA-(cytosine C5)-methyltransferase has an unusually large, partially dispensable, variable region. Nucleic Acids Res. 1993 Feb 25;21(4):905–911. [PMC free article] [PubMed]
  • Taron CH, Van Cott EM, Wilson GG, Moran LS, Slatko BE, Hornstra LJ, Benner JS, Kucera RB, Guthrie EP. Cloning and expression of the NaeI restriction endonuclease-encoding gene and sequence analysis of the NaeI restriction-modification system. Gene. 1995 Mar 21;155(1):19–25. [PubMed]
  • Studier FW, Moffatt BA. Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J Mol Biol. 1986 May 5;189(1):113–130. [PubMed]
  • Kramer B, Kramer W, Fritz HJ. Different base/base mismatches are corrected with different efficiencies by the methyl-directed DNA mismatch-repair system of E. coli. Cell. 1984 Oct;38(3):879–887. [PubMed]
  • Cupples CG, Miller JH. A set of lacZ mutations in Escherichia coli that allow rapid detection of each of the six base substitutions. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5345–5349. [PubMed]
  • Aronshtam A, Marinus MG. Dominant negative mutator mutations in the mutL gene of Escherichia coli. Nucleic Acids Res. 1996 Jul 1;24(13):2498–2504. [PMC free article] [PubMed]
  • Wu TH, Marinus MG. Dominant negative mutator mutations in the mutS gene of Escherichia coli. J Bacteriol. 1994 Sep;176(17):5393–5400. [PMC free article] [PubMed]
  • Bende SM, Grafström RH. The DNA binding properties of the MutL protein isolated from Escherichia coli. Nucleic Acids Res. 1991 Apr 11;19(7):1549–1555. [PMC free article] [PubMed]
  • Doiron KM, Viau S, Koutroumanis M, Cupples CG. Overexpression of vsr in Escherichia coli is mutagenic. J Bacteriol. 1996 Jul;178(14):4294–4296. [PMC free article] [PubMed]
  • Prolla TA, Pang Q, Alani E, Kolodner RD, Liskay RM. MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast. Science. 1994 Aug 19;265(5175):1091–1093. [PubMed]
  • Habraken Y, Sung P, Prakash L, Prakash S. Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-PMS1 complex. Curr Biol. 1997 Oct 1;7(10):790–793. [PubMed]

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