page_title: Deoxyribozyme
section_title: Ribonucleases
hierarchical_section_title: Deoxyribozyme / Types / Ribonucleases
caption_attribution_description: English: The proposed secondary structure of the 17E Pb2+-selective DNAzyme in the trans-form (two stranded). The blue strand is the enzyme strand, the black strand is the substrate strand, the red base denotes the ribonucleotide, the cyan denotes the catalytic core, and the arrow denotes the cleavage site.
context_page_description: Deoxyribozymes, also called DNA enzymes, DNAzymes, or catalytic DNA, are DNA oligonucleotides that are capable of performing a specific chemical reaction, often but not always catalytic. This is similar to the action of other biological enzymes, such as proteins or ribozymes.
  However, in contrast to the abundance of protein enzymes in biological systems and the discovery of biological ribozymes in the 1980s,
  there is only little evidence for naturally occurring deoxyribozymes.
  Deoxyribozymes should not be confused with DNA aptamers which are oligonucleotides that selectively bind a target ligand, but do not catalyze a subsequent chemical reaction.
  With the exception of ribozymes, nucleic acid molecules within cells primarily serve as storage of genetic information due to its ability to form complementary base pairs, which allows for high-fidelity copying and transfer of genetic information. In contrast, nucleic acid molecules are more limited in their catalytic ability, in comparison to protein enzymes, to just three types of interactions: hydrogen bonding, pi stacking, and metal-ion coordination.
context_section_description: The most abundant class of deoxyribozymes are ribonucleases, which catalyze the cleavage of a ribonucleotide phosphodiester bond through a transesterification reaction, forming a 2'3'-cyclic phosphate terminus and a 5'-hydroxyl terminus.
  Ribonuclease deoxyribozymes typically undergo selection as long, single-stranded oligonucleotides which contain a single ribonucleotide base to act as the cleavage site. Once sequenced, this single-stranded "cis"-form of the deoxyribozyme can be converted to the two-stranded "trans"-form by separating the substrate domain (containing the ribonucleotide cleavage site) and the enzyme domain (containing the catalytic core) into separate strands which can hybridize through two flanking arms consisting of complementary base pairs.
  The first known deoxyribozyme was a ribonuclease, discovered in 1994 by Ronald Breaker while a postdoctoral fellow in the laboratory of Gerald Joyce at the Scripps Research Institute.
  This deoxyribozyme, later named GR-5,
  catalyzes the Pb²⁺-dependent cleavage of a single ribonucleotide phosphoester at a rate that is more than 100-fold compared to the uncatalyzed reaction.  Subsequently, additional RNA-cleaving deoxyribozymes that incorporate different metal cofactors were developed, including the Mg²⁺-dependent E2 deoxyribozyme
  and the Ca²⁺-dependent Mg5 deoxyribozyme.
  These first deoxyribozymes were unable to catalyze a full RNA substrate strand, but by incorporating the full RNA substrate strand into the selection process, deoxyribozymes which functioned with substrates consisting of either full RNA or full DNA with a single RNA base were both able to be utilized.
  The first of these more versatile deoxyribozymes, 8-17 and 10-23, are currently the most widely studied deoxyribozymes. In fact, many subsequently discovered deoxyribozymes were found to contain the same catalytic core motif as 8-17, including the previously discovered Mg5, suggesting that this motif represents the "simplest solution for the RNA cleavage problem".
  The 10-23 DNAzyme contains a 15-nucleotide catalytic core that is flanked by two substrate recognition domains. This DNAzyme cleaves complementary RNAs efficiently in a sequence specific manner between an unpaired purine and a paired pyrimidine. DNAzymes targeting AU or GU vs. GC or AC are more effective. Furthermore, the RNA cleavage rates have been shown to increase after the introduction of intercalators or the substitution of deoxyguanine with deoxyinosine at the junction of the catalytic loop. Specifically, the addition of 2’-O-methyl modifications to the catalytic proved to significantly increase the cleavage rate both in vitro and in vivo.
  
  Other notable deoxyribozyme ribonucleases are those that are highly selective for a certain cofactor. Among this group are the metal selective deoxyribozymes such as Pb²⁺-specific 17E,UO₂²⁺-specific 39E,
  and Na⁺-specific A43. First crystal structure of a DNAzyme was reported in 2016. 10-23 core based DNAzymes and the respective MNAzymes that catalyse reactions at ambient temperatures were described in 2018  and open doors for use of these nucleic acid based enzymes for many other applications without the need for heating.
  This link and this link describe the DNA molecule 5'-GGAGAACGCGAGGCAAGGCTGGGAGAAATGTGGATCACGATT-3' , which acts as a deoxyribozyme that uses light to repair a thymine dimer, using serotonin as cofactor.
caption: The trans-form (two separate strands) of the 17E DNAzyme. Most ribonuclease DNAzymes have a similar form, consisting of a separate enzyme strand (blue/cyan) and substrate strand (black). Two arms of complementary bases flank the catalytic core (cyan) on the enzyme strand and the single ribonucleotide (red) on the substrate strand. The arrow shows the ribonucleotide cleavage site.
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