%0 Journal Article
%A Genna, Vito
%A Vidossich, Pietro
%A Ippoliti, Emiliano
%A Carloni, Paolo
%A Vivo, Marco De
%T A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases
%J Journal of the American Chemical Society
%V 138
%N 44
%@ 1520-5126
%C Washington, DC
%I American Chemical Society
%M FZJ-2016-05997
%P 14592 - 14598
%D 2016
%X 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′-OH and β-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-η, 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000387625300018
%$ pmid:27530537
%R 10.1021/jacs.6b05475
%U https://juser.fz-juelich.de/record/820729