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    Martin G Marinus PHD

    TitleProfessor Emeritus
    InstitutionUniversity of Massachusetts Medical School
    DepartmentBiochemistry and Molecular Pharmacology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB
    Worcester MA 01605
    Phone508-856-3330
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentBiochemistry and Molecular Pharmacology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentBiochemistry and Molecular Pharmacology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentBacterial Genetics and Pathogenesis

        Overview 
        Narrative

        Academic Background

        B.Sc.(Hons.), 1965, PhD, Otago, New Zealand, 1968
        American Cancer Society Faculty Research Award, 1976-1981
        Visiting Professor, University of Sussex, UK 1980-1981
        Erskine Fellow, University of Canterbury, NZ 1991
        Visiting Professor, University of Goettingen, Germany 1996-1997
        Visiting Professor, Centre de Génétique Moléculaire, CNRS, Gif-sur-Yvette 2006

        http://www.drug-resistance.net/

        Photo: Martin G. Marinus Biology of Enterohemorrhagic Escherichia coli O157:H7 and Enterovirus 933W.
          Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is among the leading causes of food- and water-borne illnesses affecting humans in the U.S., Europe, and Japan. Although most EHEC infections resolve spontaneously after 5-10 days of abdominal cramping and bloody diarrhea, approximately 2-7% of cases progress to the potentially fatal hemolytic uremic syndrome due, in part, to the production of cytotoxic Shiga toxins which are capable of promoting kidney failure.
         We found that resistance to certain antibiotics in E. coli O157:H7 occurs at a higher frequency than in E. coli K-12. Whole genome sequencing is being used to find the mutations responsible.
         In EHEC strain EDL933, the genes (stx2AB) encoding Shiga toxin are located on prophage 933W in the late region between genes Q and S and are transcribed with the late region genes from promoter PR’. Previous work showed that the ends of the genome in a free phage population could not be sequenced suggesting that they are terminally redundant. If so, then 933W should be able to carry out transduction of host genes from one bacterium to another. We showed that, indeed, this is the case thereby providing another way to transfer genetic material among EHEC strains.

         

         

        Formation of F-actin in HeLa cells by Escherichia coli 0157:H7. A HeLa cell infected with dam mutant bacteria of E. coli 0157:H7 is shown stained with DAPI (bacteria), filamentous actin stain (pedestals) and a merged image..

         

        Resources

         

        Oligonucleotide array transcription data

        Working with dam and dcm strains

        Bacterial Strains and Plasmids - no longer available

        Owing to circumstances beyond my control, bacterial strains and plasmids are no longer available. Please contact the E. coli Genetic Stock Center which may be able to help you with bacterial strains. Addgene may be able to provide plasmids.

         

        Microarray Analysis

        Microarray results show that global gene expression in a seqA mutant strain (left panel) is the same as that in a wildtype strain overproducing the Dam methyltransferase (center panel) but that neither is similar to that for the dam mutant (right panel).

         



        Bibliographic 
        selected publications
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        1. Marinus MG, Løbner-Olesen A. DNA Methylation. Ecosal Plus. 2014 Jun 6; 2014.
          View in: PubMed
        2. Carone BR, Xu T, Murphy KC, Marinus MG. High incidence of multiple antibiotic resistant cells in cultures of in enterohemorrhagic Escherichia coli O157:H7. Mutat Res. 2014 Jan; 759:1-8.
          View in: PubMed
        3. Groothuizen FS, Fish A, Petoukhov MV, Reumer A, Manelyte L, Winterwerp HH, Marinus MG, Lebbink JH, Svergun DI, Friedhoff P, Sixma TK. Using stable MutS dimers and tetramers to quantitatively analyze DNA mismatch recognition and sliding clamp formation. Nucleic Acids Res. 2013 Sep; 41(17):8166-81.
          View in: PubMed
        4. Jakobsen H, Bojer MS, Marinus MG, Xu T, Struve C, Krogfelt KA, Løbner-Olesen A. The alkaloid compound harmane increases the lifespan of Caenorhabditis elegans during bacterial infection, by modulating the nematode's innate immune response. PLoS One. 2013; 8(3):e60519.
          View in: PubMed
        5. Marinus MG, Poteete AR. High efficiency generalized transduction in Escherichia coli O157:H7. F1000Res. 2013; 2.
          View in: PubMed
        6. Marinus, M.G. DNA Mismatch Repair. EcoSal-Escherichia coli and Salmonella: cellular and molecular biology. A. Böck, R. Curtiss III, J. B. Kaper, P. D. Karp, F. C. Neidhardt, T. Nyström, J. M. Slauch, C. L. Squires, and D. Ussery (ed.). 2012.
        7. Murphy KC, Marinus MG. RecA-independent single-stranded DNA oligonucleotide-mediated mutagenesis. F1000 Biol Rep. 2010 Jul 22; 2:56.
          View in: PubMed
        8. Marinus MG. DNA methylation and mutator genes in Escherichia coli K-12. Mutat Res. 2010 Oct; 705(2):71-6.
          View in: PubMed
        9. Marinus MG, Løbner-Olesen A. DNA Methylation. EcoSal Plus. 2009 Aug; 3(2).
          View in: PubMed
        10. Marinus MG, Casadesus J. Roles of DNA adenine methylation in host-pathogen interactions: mismatch repair, transcriptional regulation, and more. FEMS Microbiol Rev. 2009 May; 33(3):488-503.
          View in: PubMed
        11. Løbner-Olesen A, Slominska-Wojewodzka M, Hansen FG, Marinus MG. DnaC inactivation in Escherichia coli K-12 induces the SOS response and expression of nucleotide biosynthesis genes. PLoS One. 2008 Aug 20; 3(8):e2984.
          View in: PubMed
        12. Murphy KC, Ritchie JM, Waldor MK, Løbner-Olesen A, Marinus MG. Dam methyltransferase is required for stable lysogeny of the Shiga toxin (Stx2)-encoding bacteriophage 933W of enterohemorrhagic Escherichia coli O157:H7. J Bacteriol. 2008 Jan; 190(1):438-41.
          View in: PubMed
        13. Nowosielska A, Marinus MG. DNA mismatch repair-induced double-strand breaks. DNA Repair (Amst). 2008 Jan 1; 7(1):48-56.
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        14. Broadbent SE, Balbontin R, Casadesus J, Marinus MG, van der Woude M. YhdJ, a nonessential CcrM-like DNA methyltransferase of Escherichia coli and Salmonella enterica. J Bacteriol. 2007 Jun; 189(11):4325-7.
          View in: PubMed
        15. Campellone KG, Roe AJ, Løbner-Olesen A, Murphy KC, Magoun L, Brady MJ, Donohue-Rolfe A, Tzipori S, Gally DL, Leong JM, Marinus MG. Increased adherence and actin pedestal formation by dam-deficient enterohaemorrhagic Escherichia coli O157:H7. Mol Microbiol. 2007 Mar; 63(5):1468-81.
          View in: PubMed
        16. Riber L, Olsson JA, Jensen RB, Skovgaard O, Dasgupta S, Marinus MG, Løbner-Olesen A. Hda-mediated inactivation of the DnaA protein and dnaA gene autoregulation act in concert to ensure homeostatic maintenance of the Escherichia coli chromosome. Genes Dev. 2006 Aug 1; 20(15):2121-34.
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        17. Nowosielska A, Smith SA, Engelward BP, Marinus MG. Homologous recombination prevents methylation-induced toxicity in Escherichia coli. Nucleic Acids Res. 2006; 34(8):2258-68.
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        18. López de Saro FJ, Marinus MG, Modrich P, O'Donnell M. The beta sliding clamp binds to multiple sites within MutL and MutS. J Biol Chem. 2006 May 19; 281(20):14340-9.
          View in: PubMed
        19. Calmann MA, Marinus MG. Differential effects of cisplatin and MNNG on dna mutants of Escherichia coli. Mutat Res. 2005 Oct 15; 578(1-2):406-16.
          View in: PubMed
        20. Robbins-Manke JL, Zdraveski ZZ, Marinus M, Essigmann JM. Analysis of global gene expression and double-strand-break formation in DNA adenine methyltransferase- and mismatch repair-deficient Escherichia coli. J Bacteriol. 2005 Oct; 187(20):7027-37.
          View in: PubMed
        21. Calmann MA, Nowosielska A, Marinus MG. The MutS C terminus is essential for mismatch repair activity in vivo. J Bacteriol. 2005 Sep; 187(18):6577-9.
          View in: PubMed
        22. Nowosielska A, Marinus MG. Cisplatin induces DNA double-strand break formation in Escherichia coli dam mutants. DNA Repair (Amst). 2005 Jul 12; 4(7):773-81.
          View in: PubMed
        23. Calmann MA, Evans JE, Marinus MG. MutS inhibits RecA-mediated strand transfer with methylated DNA substrates. Nucleic Acids Res. 2005; 33(11):3591-7.
          View in: PubMed
        24. Løbner-Olesen A, Skovgaard O, Marinus MG. Dam methylation: coordinating cellular processes. Curr Opin Microbiol. 2005 Apr; 8(2):154-60.
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        25. Calmann MA, Nowosielska A, Marinus MG. Separation of mutation avoidance and antirecombination functions in an Escherichia coli mutS mutant. Nucleic Acids Res. 2005; 33(4):1193-200.
          View in: PubMed
        26. Calmann MA, Marinus MG. MutS inhibits RecA-mediated strand exchange with platinated DNA substrates. Proc Natl Acad Sci U S A. 2004 Sep 28; 101(39):14174-9.
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        27. Nowosielska A, Calmann MA, Zdraveski Z, Essigmann JM, Marinus MG. Spontaneous and cisplatin-induced recombination in Escherichia coli. DNA Repair (Amst). 2004 Jul 2; 3(7):719-28.
          View in: PubMed
        28. Calmann MA, Marinus MG. Regulated expression of the Escherichia coli dam gene. J Bacteriol. 2003 Aug; 185(16):5012-4.
          View in: PubMed
        29. Løbner-Olesen A, Marinus MG, Hansen FG. Role of SeqA and Dam in Escherichia coli gene expression: a global/microarray analysis. Proc Natl Acad Sci U S A. 2003 Apr 15; 100(8):4672-7.
          View in: PubMed
        30. Roberts RJ, Belfort M, Bestor T, Bhagwat AS, Bickle TA, Bitinaite J, Blumenthal RM, Degtyarev SKh, Dryden DT, Dybvig K, Firman K, Gromova ES, Gumport RI, Halford SE, Hattman S, Heitman J, Hornby DP, Janulaitis A, Jeltsch A, Josephsen J, Kiss A, Klaenhammer TR, Kobayashi I, Kong H, Krüger DH, Lacks S, Marinus MG, Miyahara M, Morgan RD, Murray NE, Nagaraja V, Piekarowicz A, Pingoud A, Raleigh E, Rao DN, Reich N, Repin VE, Selker EU, Shaw PC, Stein DC, Stoddard BL, Szybalski W, Trautner TA, Van Etten JL, Vitor JM, Wilson GG, Xu SY. A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes. Nucleic Acids Res. 2003 Apr 1; 31(7):1805-12.
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        31. Wu TH, Loh T, Marinus MG. The function of Asp70, Glu77 and Lys79 in the Escherichia coli MutH protein. Nucleic Acids Res. 2002 Feb 1; 30(3):818-22.
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        32. Spek EJ, Wright TL, Stitt MS, Taghizadeh NR, Tannenbaum SR, Marinus MG, Engelward BP. Recombinational repair is critical for survival of Escherichia coli exposed to nitric oxide. J Bacteriol. 2001 Jan; 183(1):131-8.
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        33. Loh T, Murphy KC, Marinus MG. Mutational analysis of the MutH protein from Escherichia coli. J Biol Chem. 2001 Apr 13; 276(15):12113-9.
          View in: PubMed
        34. Vaisvila R, Rasmussen LJ, Lobner-Olesen A, von Freiesleben U, Marinus MG. The LipB protein is a negative regulator of dam gene expression in Escherichia coli. Biochim Biophys Acta. 2000 Nov 15; 1494(1-2):43-53.
          View in: PubMed
        35. Zdraveski ZZ, Mello JA, Marinus MG, Essigmann JM. Multiple pathways of recombination define cellular responses to cisplatin. Chem Biol. 2000 Jan; 7(1):39-50.
          View in: PubMed
        36. Marinus MG. Recombination is essential for viability of an Escherichia coli dam (DNA adenine methyltransferase) mutant. J Bacteriol. 2000 Jan; 182(2):463-8.
          View in: PubMed
        37. Wu TH, Marinus MG. Deletion mutation analysis of the mutS gene in Escherichia coli. J Biol Chem. 1999 Feb 26; 274(9):5948-52.
          View in: PubMed
        38. Horst JP, Wu TH, Marinus MG. Escherichia coli mutator genes. Trends Microbiol. 1999 Jan; 7(1):29-36.
          View in: PubMed
        39. Drotschmann K, Aronshtam A, Fritz HJ, Marinus MG. The Escherichia coli MutL protein stimulates binding of Vsr and MutS to heteroduplex DNA. Nucleic Acids Res. 1998 Feb 15; 26(4):948-53.
          View in: PubMed
        40. Aronshtam A, Marinus MG. Dominant negative mutator mutations in the mutL gene of Escherichia coli. Nucleic Acids Res. 1996 Jul 1; 24(13):2498-504.
          View in: PubMed
        41. Rasmussen LJ, Løbner-Olesen A, Marinus MG. Growth-rate-dependent transcription initiation from the dam P2 promoter. Gene. 1995 May 19; 157(1-2):213-5.
          View in: PubMed
        42. Wu TH, Marinus MG. Dominant negative mutator mutations in the mutS gene of Escherichia coli. J Bacteriol. 1994 Sep; 176(17):5393-400.
          View in: PubMed
        43. Palmer BR, Marinus MG. The dam and dcm strains of Escherichia coli--a review. Gene. 1994 May 27; 143(1):1-12.
          View in: PubMed
        44. Rasmussen LJ, Marinus MG, Løbner-Olesen A. Novel growth rate control of dam gene expression in Escherichia coli. Mol Microbiol. 1994 May; 12(4):631-8.
          View in: PubMed
        45. Carraway M, Marinus MG. Repair of heteroduplex DNA molecules with multibase loops in Escherichia coli. J Bacteriol. 1993 Jul; 175(13):3972-80.
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        46. Foster PL, Marinus MG. Levels of epsilon, an essential replication subunit of Escherichia coli DNA polymerase III, are controlled by heat shock proteins. J Bacteriol. 1992 Dec; 174(23):7509-16.
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        47. Løbner-Olesen A, Boye E, Marinus MG. Expression of the Escherichia coli dam gene. Mol Microbiol. 1992 Jul; 6(13):1841-51.
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        48. Wu TH, Grelland E, Boye E, Marinus MG. Identification of a weak promoter for the dam gene of Escherichia coli. Biochim Biophys Acta. 1992 May 7; 1131(1):47-52.
          View in: PubMed
        49. 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):1730-4.
          View in: PubMed
        50. Boye E, Marinus MG, Løbner-Olesen A. Quantitation of Dam methyltransferase in Escherichia coli. J Bacteriol. 1992 Mar; 174(5):1682-5.
          View in: PubMed
        51. Løbner-Olesen A, Marinus MG. Identification of the gene (aroK) encoding shikimic acid kinase I of Escherichia coli. J Bacteriol. 1992 Jan; 174(2):525-9.
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        52. Boe L, Marinus MG. Role of plasmid multimers in mutation to tetracycline resistance. Mol Microbiol. 1991 Oct; 5(10):2541-5.
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        53. Palmer BR, Marinus MG. DNA methylation alters the pattern of spontaneous mutation in Escherichia coli cells (mutD) defective in DNA polymerase III proofreading. Mutat Res. 1991 Sep; 264(1):15-23.
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        54. Carraway M, Rewinski C, Marinus MG. Mutations produced by DNA polymerase III holoenzyme of Escherichia coli after in vitro synthesis in the absence of single-strand binding protein. Mol Microbiol. 1990 Oct; 4(10):1645-52.
          View in: PubMed
        55. Wu TH, Clarke CH, Marinus MG. Specificity of Escherichia coli mutD and mutL mutator strains. Gene. 1990 Mar 1; 87(1):1-5.
          View in: PubMed
        56. Fram RJ, Mack SL, George M, Marinus MG. DNA repair mechanisms affecting cytotoxicity by streptozotocin in E. coli. Mutat Res. 1989 Sep; 218(2):125-33.
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        57. Barras F, Marinus MG. The great GATC: DNA methylation in E. coli. Trends Genet. 1989 May; 5(5):139-43.
          View in: PubMed
        58. Carraway M, Rewinski C, Wu TH, Marinus MG. Specificity of the Dam-directed mismatch repair system of Escherichia coli K-12. Gene. 1988 Dec 25; 74(1):157-8.
          View in: PubMed
        59. Parker B, Marinus MG. A simple and rapid method to obtain substitution mutations in Escherichia coli: isolation of a dam deletion/insertion mutation. Gene. 1988 Dec 20; 73(2):531-5.
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        60. Mack SL, Fram RJ, Marinus MG. Sequence specificity of streptozotocin-induced mutations. Nucleic Acids Res. 1988 Oct 25; 16(20):9811-20.
          View in: PubMed
        61. Barras F, Marinus MG. Arrangement of Dam methylation sites (GATC) in the Escherichia coli chromosome. Nucleic Acids Res. 1988 Oct 25; 16(20):9821-38.
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        62. Fram RJ, Marinus MG, Volkert MR. Gene expression in E. coli after treatment with streptozotocin. Mutat Res. 1988 Mar; 198(1):45-51.
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        63. Rewinski C, Marinus MG. Mutation spectrum in Escherichia coli DNA mismatch repair deficient (mutH) strain. Nucleic Acids Res. 1987 Oct 26; 15(20):8205-15.
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        64. Carraway M, Youderian P, Marinus MG. Spontaneous mutations occur near dam recognition sites in a dam- Escherichia coli host. Genetics. 1987 Jul; 116(3):343-7.
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        65. Marinus MG. DNA methylation in Escherichia coli. Annu Rev Genet. 1987; 21:113-31.
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        66. Fram RJ, Sullivan J, Marinus MG. Mutagenesis and repair of DNA damage caused by nitrogen mustard, N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), streptozotocin, and mitomycin C in E. coli. Mutat Res. 1986 Nov; 166(3):299-42.
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        67. Lucchesi P, Carraway M, Marinus MG. Analysis of forward mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine in the bacteriophage P22 mnt repressor gene. J Bacteriol. 1986 Apr; 166(1):34-7.
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        68. Schlagman SL, Hattman S, Marinus MG. Direct role of the Escherichia coli Dam DNA methyltransferase in methylation-directed mismatch repair. J Bacteriol. 1986 Mar; 165(3):896-900.
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        69. Fram RJ, Cusick PS, Marinus MG. Studies on mutagenesis and repair induced by platinum analogs. Mutat Res. 1986 Jan; 173(1):13-8.
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        70. Fram RJ, Cusick PS, Wilson JM, Marinus MG. Mismatch repair of cis-diamminedichloroplatinum(II)-induced DNA damage. Mol Pharmacol. 1985 Jul; 28(1):51-5.
          View in: PubMed
        71. Marinus MG. DNA methylation influences trpR promoter activity in Escherichia coli K-12. Mol Gen Genet. 1985; 200(1):185-6.
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        72. Peterson KR, Wertman KF, Mount DW, Marinus MG. Viability of Escherichia coli K-12 DNA adenine methylase (dam) mutants requires increased expression of specific genes in the SOS regulon. Mol Gen Genet. 1985; 201(1):14-9.
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        73. Marinus MG, Poteete A, Arraj JA. Correlation of DNA adenine methylase activity with spontaneous mutability in Escherichia coli K-12. Gene. 1984 Apr; 28(1):123-5.
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        74. Craig RJ, Arraj JA, Marinus MG. Induction of damage inducible (SOS) repair in dam mutants of Escherichia coli exposed to 2-aminopurine. Mol Gen Genet. 1984; 194(3):539-40.
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        75. Arraj JA, Marinus MG. Phenotypic reversal in dam mutants of Escherichia coli K-12 by a recombinant plasmid containing the dam+ gene. J Bacteriol. 1983 Jan; 153(1):562-5.
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        76. Marinus MG, Carraway M, Frey AZ, Brown L, Arraj JA. Insertion mutations in the dam gene of Escherichia coli K-12. Mol Gen Genet. 1983; 192(1-2):288-9.
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        77. Karran P, Marinus MG. Mismatch correction at O6-methylguanine residues in E. coli DNA. Nature. 1982 Apr 29; 296(5860):868-9.
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        78. McGraw BR, Marinus MG. Isolation and characterization of Dam+ revertants and suppressor mutations that modify secondary phenotypes of dam-3 strains of Escherichia coli K-12. Mol Gen Genet. 1980; 178(2):309-15.
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        79. Marinus MG. Influence of uvrD3, uvrE502, and recL152 mutations on the phenotypes of Escherichia coli K-12 dam mutants. J Bacteriol. 1980 Jan; 141(1):223-6.
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        80. Bale A, d'Alarcao M, Marinus MG. Characterization of DNA adenine methylation mutants of Escherichia coli K12. Mutat Res. 1979 Feb; 59(2):157-65.
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        81. Marinus MG, Konrad EB. Hyper-recombination in dam mutants of Escherichia coli K-12. Mol Gen Genet. 1976 Dec 22; 149(3):273-7.
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        82. Marinus MG. Adenine methylation of Okazaki fragments in Escherichia coli. J Bacteriol. 1976 Dec; 128(3):853-4.
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        83. Marinus MG, Morris NR, Söll D, Kwong TC. Isolation and partial characterization of three Escherichia coli mutants with altered transfer ribonucleic acid methylases. J Bacteriol. 1975 Apr; 122(1):257-65.
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        84. Marinus MG, Morris NR. Pleiotropic effects of a DNA adenine methylation mutation (dam-3) in Escherichia coli K12. Mutat Res. 1975 Apr; 28(1):15-26.
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        85. Marinus MG, Morris NR. Biological function for 6-methyladenine residues in the DNA of Escherichia coli K12. J Mol Biol. 1974 May 15; 85(2):309-22.
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        86. Marinus MG, Morris NR. Isolation of deoxyribonucleic acid methylase mutants of Escherichia coli K-12. J Bacteriol. 1973 Jun; 114(3):1143-50.
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        87. Van Hartingsveldt J, Marinus MG, Stouthamer AH. Mutants of Pseudomonas aeruginosa bblocked in nitrate or nitrite dissimilation. Genetics. 1971 Apr; 67(4):469-82.
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        88. Marinus MG, Adelberg EA. Vegetative Replication and Transfer Replication of Deoxyribonucleic Acid in Temperature-Sensitive Mutants of Escherichia coli K-12. J Bacteriol. 1970 Dec; 104(3):1266-72.
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        89. Marinus MG, Loutit JS. Regulation of isoleucine-valine biosynthesis in Pseudomonas aeruginosa. II. Regulation of enzyme activity and synthesis. Genetics. 1969 Nov; 63(3):557-67.
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        90. Marinus MG, Loutit JS. Regulation of isoleucine-valine biosynthesis in Pseudomonas aeruginosa. I. Characterisation and mapping of mutants. Genetics. 1969 Nov; 63(3):547-56.
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        91. Loutit JS, Marinus MG, Pearce LE. Investigation of the mating system of Pseudomonas aeruginosa strain 1. 3. Kinetic studies on the transfer of the sex factor (FP). Genet Res. 1968 Oct; 12(2):139-45.
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        92. Loutit JS, Marinus MG. Investigation of the mating system of Pseudomonas aeruginosa strain 1. II. Mapping of a number of early markers. Genet Res. 1968 Aug; 12(1):37-44.
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        93. Loutit JS, Pearce LE, Marinus MG. Investigation of the mating system of Pseudomonas aeruginosa strain 1. I. Kinetic studies. Genet Res. 1968 Aug; 12(1):29-36.
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