Medical Biochemistry - Nucleic Acids

Summary

Nucleic acids lie at the heart of cellular function, carrying genetic information and mediating its faithful expression and preservation. Deoxyribonucleic acid (DNA) is the long‐term repository of hereditary data, packaged within chromatin and chromosomes, while ribonucleic acid (RNA) implements and regulates gene expression through messenger, transfer and ribosomal species and by a growing family of non‐coding RNAs. The chemical integrity of DNA is continually challenged by endogenous and exogenous insults—reactive oxygen species, hydrolytic attack and mutagenic chemicals—prompting sophisticated repair systems such as base excision, nucleotide excision and mismatch repair. Equally, the fidelity of DNA replication depends on precise control of ribonucleotide incorporation and removal by ribonuclease H–dependent pathways. In clinical practice, synthetic nucleoside and nucleotide analogues exploit the biochemistry of polymerases and repair enzymes to inhibit viral replication and target malignancies. Advances in our understanding of nucleic acid damage sensing, enzymatic excision and tolerance mechanisms underpin diagnostics and the development of new therapies across infectious, inflammatory and neoplastic diseases.

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Medical Biochemistry - Nucleic Acids publication trend

The graph below shows the total number of articles in medical biochemistry - nucleic acids across all publications each year (not limited to Nature Index journals).

Technical terms

Nucleoside analogue: A synthetic compound resembling a natural nucleoside, designed to disrupt nucleic acid metabolism by incorporation into DNA or RNA.

Reactive oxygen species (ROS): Highly reactive oxygen‐derived radicals that can oxidise nucleobases and the sugar–phosphate backbone.

8-oxo-7,8-dihydroguanine (8-oxoG): A common oxidative lesion of guanine that mispairs with adenine, leading to G→T transversion mutations.

Base excision repair (BER): A multistep pathway in which a DNA glycosylase removes a damaged base, followed by end processing, gap filling and ligation.

Ribonucleotide excision repair (RER): A mechanism that identifies and removes ribonucleotides misincorporated into DNA, primarily via RNase H2‐mediated cleavage.

RNase H2: An enzyme complex that cleaves the RNA strand of RNA–DNA hybrids and excises isolated ribonucleotides embedded in DNA.

Prodrug: An inactive precursor that is enzymatically converted in vivo to release the active therapeutic agent.

References

  1. New insights into the synergism of nucleoside analogs with radiotherapy. Radiation Oncology (2013).
  2. Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides. Medicinal Research Reviews (2017).
  3. OH Radical‐Induced Oxidation in Nucleosides and Nucleotides Unraveled by Tandem Mass Spectrometry and Infrared Multiple Photon Dissociation Spectroscopy. ChemPhysChem (2023).
  4. Type I and Type II photosensitization of DNA etheno adducts. Photochemical & Photobiological Sciences (2024).
  5. Detection of ribonucleotides embedded in DNA by Nanopore sequencing. Communications Biology (2024).
  6. RTF2 controls replication repriming and ribonucleotide excision at the replisome. Nature Communications (2024).

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