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Related Concept Videos

DNA Topoisomerases02:02

DNA Topoisomerases

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Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
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DNA Damage can Stall the Cell Cycle02:36

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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DNA Damage Can Stall the Cell Cycle02:36

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Inhibitors of Bacterial DNA Synthesis01:28

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Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These...
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DNA Helicases00:55

DNA Helicases

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DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
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Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

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For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
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Tools to Study the Role of Architectural Protein HMGB1 in the Processing of Helix Distorting, Site-specific DNA Interstrand Crosslinks
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Os2 -Os4 Switch Controls DNA Knotting and Anticancer Activity.

Ying Fu1,2, María J Romero1,3, Luca Salassa1,4

  • 1Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.

Angewandte Chemie (International Ed. in English)
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New osmium-arene complexes show strong anticancer activity by knotting DNA. Shorter linkers decrease effectiveness, but DNA condensation behavior correlates with biological impact.

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Area of Science:

  • Organometallic Chemistry
  • Medicinal Chemistry
  • Biophysical Chemistry

Background:

  • Dinuclear trihydroxido-bridged osmium-arene complexes are typically inert and biologically inactive.
  • Osmium(II)-arene complexes are explored for potential therapeutic applications.

Purpose of the Study:

  • To investigate the antiproliferative activity of novel metallacycle frameworks formed by linking osmium-arene fragments.
  • To explore the relationship between complex structure, DNA interaction, and biological activity.

Main Methods:

  • Synthesis of dihydroxido-bridged Os(II)-arene fragments linked by a bridging di-imine.
  • Assessment of antiproliferative activity against cancer cells.
  • Analysis of DNA condensation behavior using plasmid DNA.

Main Results:

  • The metallacycle framework exhibits strong antiproliferative activity against cancer cells.
  • DNA knotting was observed, a novel interaction for these types of complexes.
  • Reduced spacer length decreased both biological activity and solution stability.
  • Differences in plasmid DNA condensation correlated significantly with observed biological activity.

Conclusions:

  • Metallacycle formation from osmium-arene fragments can yield potent anticancer agents.
  • DNA knotting and condensation are key mechanisms underlying the biological activity.
  • Structural modifications, such as spacer length, critically influence efficacy and stability.