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Related Concept Videos

Mismatch Repair01:20

Mismatch Repair

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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
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The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
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Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis
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Targeting DNA mismatches with metal complexes.

Natália Kolozsvári1, Martin R Gill1

  • 1Department of Chemistry, Faculty of Science and Engineering, Swansea University, Swansea, UK.

Journal of Inorganic Biochemistry
|July 1, 2025
PubMed
Summary

Metal complexes can target persistent DNA mismatches in MMR-deficient cancers. This offers a new strategy for developing targeted cancer therapeutics and advanced imaging agents.

Keywords:
MMR-deficient cancerMismatch DNAPlatinumRhodiumRuthenium

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Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Cancer Research

Background:

  • DNA mismatches, non-canonical base pairs, arise from replication errors or DNA damage.
  • The mismatch repair (MMR) pathway normally corrects these errors.
  • MMR deficiency in cancers (e.g., colorectal, endometrial) leads to persistent DNA mismatches, creating a therapeutic vulnerability.

Purpose of the Study:

  • To review the potential of metal complexes in targeting DNA mismatches.
  • To explore the use of rhodium(III), ruthenium(II), and platinum(II) complexes for selective DNA mismatch binding.
  • To discuss applications in next-generation therapeutics and imaging probes.

Main Methods:

  • Review of existing literature on metal complexes and DNA interactions.
  • Analysis of structural, electronic, and photophysical properties of metal complexes.
  • Discussion of ligand design strategies for selective DNA binding.

Main Results:

  • Metal complexes with rhodium(III), ruthenium(II), and platinum(II) centers can preferentially bind to DNA mismatches.
  • These complexes offer opportunities for differentiating between canonical and mismatched DNA.
  • Ligand design is crucial for achieving high selectivity and desired properties.

Conclusions:

  • Metal complexes represent a promising foundation for developing novel therapeutics and imaging agents targeting DNA mismatches.
  • Exploiting the unique properties of metal complexes can lead to highly selective agents for MMR-deficient cancers.
  • Further research into metal complex-DNA interactions can advance precision medicine and diagnostics.