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@ARTICLE{Genna:820729,
author = {Genna, Vito and Vidossich, Pietro and Ippoliti, Emiliano
and Carloni, Paolo and Vivo, Marco De},
title = {{A} {S}elf-{A}ctivated {M}echanism for {N}ucleic {A}cid
{P}olymerization {C}atalyzed by {DNA}/{RNA} {P}olymerases},
journal = {Journal of the American Chemical Society},
volume = {138},
number = {44},
issn = {1520-5126},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {FZJ-2016-05997},
pages = {14592 - 14598},
year = {2016},
abstract = {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.},
cin = {IAS-5 / INM-9},
ddc = {540},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {899 - ohne Topic (POF3-899)},
pid = {G:(DE-HGF)POF3-899},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000387625300018},
pubmed = {pmid:27530537},
doi = {10.1021/jacs.6b05475},
url = {https://juser.fz-juelich.de/record/820729},
}