Nucleases: diversity of structure, function and mechanism
TLDR
This review surveys nuclease activities with known structures and catalytic machinery and classify them by reaction mechanism and metal-ion dependence and by their biological function ranging from DNA replication, recombination, repair, RNA maturation, processing, interference, to defense, nutrient regeneration or cell death.Abstract:
Nucleases cleave the phosphodiester bonds of nucleic acids and may be endo or exo, DNase or RNase, topoisomerases, recombinases, ribozymes, or RNA splicing enzymes. In this review, I survey nuclease activities with known structures and catalytic machinery and classify them by reaction mechanism and metal-ion dependence and by their biological function ranging from DNA replication, recombination, repair, RNA maturation, processing, interference, to defense, nutrient regeneration or cell death. Several general principles emerge from this analysis. There is little correlation between catalytic mechanism and biological function. A single catalytic mechanism can be adapted in a variety of reactions and biological pathways. Conversely, a single biological process can often be accomplished by multiple tertiary and quaternary folds and by more than one catalytic mechanism. Two-metal-ion-dependent nucleases comprise the largest number of different tertiary folds and mediate the most diverse set of biological functions. Metal-ion-dependent cleavage is exclusively associated with exonucleases producing mononucleotides and endonucleases that cleave double- or single-stranded substrates in helical and base-stacked conformations. All metal-ion-independent RNases generate 2',3'-cyclic phosphate products, and all metal-ion-independent DNases form phospho-protein intermediates. I also find several previously unnoted relationships between different nucleases and shared catalytic configurations.read more
Citations
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Structures of Cas9 Endonucleases Reveal RNA- Mediated Conformational Activation
Martin Jinek,Fuguo Jiang,David W. Taylor,David W. Taylor,Samuel H. Sternberg,Emine Kaya,Enbo Ma,Carolin Anders,Michael H. Hauer,Kaihong Zhou,Steven Lin,Matias Kaplan,Anthony T. Iavarone,Emmanuelle Charpentier,Emmanuelle Charpentier,Eva Nogales,Jennifer A. Doudna +16 more
TL;DR: To compare the architectures and domain organization of diverse Cas9 proteins, the atomic structures of Cas9 from Streptococcus pyogenes and Actinomyces naeslundii and AnaCas9 were determined by x-ray crystallography and three-dimensional reconstructions of apo-SpyCas9, SpyCas9:RNA, and SpyCas 9:RNA:DNA were obtained by negative-stain single-particle electron microscopy.
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Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection
Alexandra East-Seletsky,Mitchell R. O’Connell,Spencer C. Knight,David Burstein,Jamie H. D. Cate,Jamie H. D. Cate,Robert Tjian,Jennifer A. Doudna +7 more
TL;DR: It is shown that bacterial C2c2 possesses a unique RNase activity responsible for CRISPR RNA maturation that is distinct from its RNA-activated single-stranded RNA degradation activity.
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CRISPR-Mediated Adaptive Immune Systems in Bacteria and Archaea
TL;DR: The mechanisms of CRISPR-mediated immunity are reviewed and the ecological and evolutionary implications of these adaptive defense systems are discussed.
Journal ArticleDOI
Polymorphic toxin systems: comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics
Dapeng Zhang,Robson Francisco de Souza,Robson Francisco de Souza,Vivek Anantharaman,Lakshminarayan M. Iyer,L. Aravind +5 more
TL;DR: Gene-neighborhood-analysis of polymorphic toxin systems predicts the presence of novel trafficking-related components, and also the organizational logic that allows toxin diversification through recombination, and several testable predictions regarding active sites and catalytic mechanisms are presented.
Journal ArticleDOI
SimRNA: a coarse-grained method for RNA folding simulations and 3D structure prediction
Michal J. Boniecki,Grzegorz Lach,Wayne K. Dawson,Konrad Tomala,Pawel Lukasz,Tomasz Sołtysiński,Kristian Rother,Janusz M. Bujnicki +7 more
TL;DR: SimRNA is presented, a new method for computational RNA 3D structure prediction, which uses a coarse-grained representation, relies on the Monte Carlo method for sampling the conformational space, and employs a statistical potential to approximate the energy and identify conformations that correspond to biologically relevant structures.
References
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