Blackstock, Chelsea, Walters-Freke, Caitlin, Richards, Nigel  ORCID: https://orcid.org/0000-0002-0375-0881 and Williamson, Adele
2025.
Nucleic acid joining enzymes: biological functions and synthetic applications beyond DNA.
Biochemical Journal
482
(2)
, pp. 39-56.
10.1042/BCJ20240136
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Abstract
DNA-joining by ligase and polymerase enzymes has provided the foundational tools for generating recombinant DNA and enabled the assembly of gene and genome-sized synthetic products. Xenobiotic nucleic acid (XNA) analogues of DNA and RNA with alternatives to the canonical bases, so-called ‘unnatural’ nucleobase pairs (UBP-XNAs), represent the next frontier of nucleic acid technologies, with applications as novel therapeutics and in engineering semi-synthetic biological organisms. To realise the full potential of UBP-XNAs, researchers require a suite of compatible enzymes for processing nucleic acids on a par with those already available for manipulating canonical DNA. In particular, enzymes able to join UBP-XNA will be essential for generating large assemblies and also hold promise in the synthesis of single-stranded oligonucleotides. Here, we review recent and emerging advances in the DNA-joining enzymes, DNA polymerases and DNA ligases, and describe their applications to UBP-XNA manipulation. We also discuss the future directions of this field which we consider will involve two-pronged approaches of enzyme biodiscovery for natural UBP-XNA compatible enzymes, coupled with improvement by structure-guided engineering.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | Published |
| Schools: | Schools > Chemistry |
| Publisher: | Portland Press |
| ISSN: | 0264-6021 |
| Funders: | BBSRC |
| Date of First Compliant Deposit: | 26 March 2025 |
| Date of Acceptance: | 4 December 2024 |
| Last Modified: | 27 Mar 2025 11:30 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/177187 |
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