Structural highlights
Function
DPOLX_ASFB7 Error-prone polymerase lacking a proofreading 3'-5' exonuclease which plays a role in viral DNA repair. Specifically binds intermediates in the single-nucleotide base-excision repair process. Also catalyzes DNA polymerization with low nucleotide-insertion fidelity. Together with the viral DNA ligase, fills the single nucleotide gaps generated by the AP endonuclease.[1] [2]
Publication Abstract from PubMed
Deoxyribozymes (DNAzymes) are in vitro evolved DNA sequences capable of catalyzing chemical reactions. The RNA-cleaving 10-23 DNAzyme was the first DNAzyme to be evolved and possesses clinical and biotechnical applications as a biosensor and a knockdown agent. DNAzymes do not require the recruitment of other components to cleave RNA and can turnover, thus they have a distinct advantage over other knockdown methods (siRNA, CRISPR, morpholinos). Despite this, a lack of structural and mechanistic information has hindered the optimization and application of the 10-23 DNAzyme. Here, we report a 2.7 A crystal structure of the RNA-cleaving 10-23 DNAzyme in a homodimer conformation. Although proper coordination of the DNAzyme to substrate is observed along with intriguing patterns of bound magnesium ions, the dimer conformation likely does not capture the true catalytic form of the 10-23 DNAzyme.
Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation.,Cramer ER, Starcovic SA, Avey RM, Kaya AI, Robart AR Commun Chem. 2023 Jun 10;6(1):119. doi: 10.1038/s42004-023-00924-3. PMID:37301907[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Garcia-Escudero R, Garcia-Diaz M, Salas ML, Blanco L, Salas J. DNA polymerase X of African swine fever virus: insertion fidelity on gapped DNA substrates and AP lyase activity support a role in base excision repair of viral DNA. J Mol Biol. 2003 Mar 7;326(5):1403-12. PMID:12595253
- ↑ Showalter AK, Byeon IJ, Su MI, Tsai MD. Solution structure of a viral DNA polymerase X and evidence for a mutagenic function. Nat Struct Biol. 2001 Nov;8(11):942-6. PMID:11685239 doi:10.1038/nsb1101-942
- ↑ Cramer ER, Starcovic SA, Avey RM, Kaya AI, Robart AR. Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation. Commun Chem. 2023 Jun 10;6(1):119. PMID:37301907 doi:10.1038/s42004-023-00924-3