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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.
Types and Mechanism of action
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An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
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Deoxyribonucleic acid, or DNA, is the genetic material responsible for passing traits from generation to generation in all organisms and most viruses. DNA is composed of two strands of nucleotides that wind around each other to form a spring-like structure called a double helix. However, the double helix is not perfectly symmetrical. Instead, there are regularly occurring grooves in the structure. The major groove occurs where the sugar-phosphate backbones are relatively far apart. This space...
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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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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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Folding and Characterization of a Bio-responsive Robot from DNA Origami
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Resolving DNA origami structural integrity and pharmacokinetics in vivo.

Yang Wang1,2,3,4, Iris Rocamonde-Lago2, Janine Waldvogel2

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A new method, proximity ligation assay for structural tracking and integrity quantification (PLASTIQ), precisely measures DNA origami integrity in vivo using minimal blood. This advances DNA nanostructures for therapeutic development.

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Molecular Engineering

Background:

  • DNA origami shows therapeutic promise but lacks in vivo structural integrity assessment methods.
  • This limitation hinders the clinical translation of DNA nanostructures for drug delivery.

Purpose of the Study:

  • To introduce a novel method for quantifying DNA origami structural integrity in vivo.
  • To enable dynamic monitoring of DNA origami degradation and evaluate stabilization strategies.

Main Methods:

  • Proximity ligation assay for structural tracking and integrity quantification (PLASTIQ) was developed.
  • PLASTIQ utilizes a small blood volume (1 µl) with high sensitivity (0.01 fM detection limit).
  • The method was applied in a murine model to track DNA origami degradation and assess PEGylation efficacy.

Main Results:

  • PLASTIQ successfully quantified DNA origami degradation dynamics in circulating blood.
  • PEGylation was observed to significantly slow down DNA origami degradation in vivo.
  • Distinct degradation rates were found for internal versus external DNA helices in a barrel-like structure.

Conclusions:

  • PLASTIQ provides a quantitative, longitudinal approach for assessing in vivo DNA origami integrity.
  • This method offers pharmaceutical-level insights crucial for accelerating DNA nanostructure-based therapeutic development.
  • Understanding degradation kinetics informs the design of more stable and effective DNA nanomedicines.