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A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases

Marco De Vivo; Marco De Vivo; Emiliano Ippoliti; Vito Genna; Vito Genna; Paolo Carloni; Pietro Vidossich


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  "doi": "10.1021/jacs.6b05475", 
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    "creators": [
      {
        "name": "Marco De Vivo"
      }, 
      {
        "name": "Marco De Vivo"
      }, 
      {
        "name": "Emiliano Ippoliti"
      }, 
      {
        "name": "Vito Genna"
      }, 
      {
        "name": "Vito Genna"
      }, 
      {
        "name": "Paolo Carloni"
      }, 
      {
        "name": "Pietro Vidossich"
      }
    ], 
    "description": "The enzymatic polymerization of DNA and RNA is the basis for genetic inheritance for all living organisms. It is catalyzed by the DNA/RNA polymerase (Pol) superfamily. Here, bioinformatics analysis reveals that the incoming nucleotide substrate always forms an H-bond between its 3\u2032-OH and \u03b2-phosphate moieties upon formation of the Michaelis complex. This previously unrecognized H-bond implies a novel self-activated mechanism (SAM), which synergistically connects the in situ nucleophile formation with subsequent nucleotide addition and, importantly, nucleic acid translocation. Thus, SAM allows an elegant and efficient closed-loop sequence of chemical and physical steps for Pol catalysis. This is markedly different from previous mechanistic hypotheses. Our proposed mechanism is corroborated via ab initio QM/MM simulations on a specific Pol, the human DNA polymerase-\u03b7, an enzyme involved in repairing damaged DNA. The structural conservation of DNA and RNA Pols supports the possible extension of SAM to Pol enzymes from the three domains of life.", 
    "doi": "10.1021/jacs.6b05475", 
    "keywords": [
      "Colloid and Surface Chemistry", 
      "Biochemistry", 
      "General Chemistry", 
      "Catalysis"
    ], 
    "language": "eng", 
    "license": {
      "id": "other-open"
    }, 
    "notes": "", 
    "publication_date": "2016-08-31", 
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      "title": "Journal article", 
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    "title": "A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases"
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