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Related Concept Videos

DNA Topoisomerases02:02

DNA Topoisomerases

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
Topoisomerases are divided into two main types.  Type I...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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, a...
Homologous Recombination02:31

Homologous Recombination

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...
The DNA Replication Fork01:02

The DNA Replication Fork

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 forks, one in...
Residual Stresses01:26

Residual Stresses

Residual stresses reside in a structure even after removing the original stress inducer. This phenomenon often arises from varied plastic deformations across different parts of a structure. Consider a rod stretched beyond its yield point. It will not regain its original length due to permanent deformation. Even after load removal, the rod does not entirely lose stress because of uneven plastic deformations, resulting in residual stresses. The computation of these stresses in structures is...
DNA as a Genetic Template02:05

DNA as a Genetic Template

Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...

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Optical Tweezers to Study RNA-Protein Interactions in Translation Regulation
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Published on: February 12, 2022

RNA unwinding from reweighted pulling simulations.

Francesco Colizzi1, Giovanni Bussi

  • 1SISSA-Scuola Internazionale Superiore di Studi Avanzati, via Bonomea 265, 34136 Trieste, Italy. colizzi@sissa.it

Journal of the American Chemical Society
|February 9, 2012
PubMed
Summary

This study reveals the molecular dynamics of RNA base pair opening and closing, crucial for biological functions. Our findings provide a motion picture of helix opening, validated by experiments, and explain enzyme-driven unwinding.

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Area of Science:

  • Molecular Biophysics
  • Computational Biology
  • RNA Biology

Background:

  • Forming and melting of RNA base pairs are essential conformational transitions for biological functions.
  • The dynamic steps of these RNA duplex transitions lack quantitative molecular-level characterization.

Purpose of the Study:

  • To quantitatively characterize the dynamic steps of RNA base pair opening and melting at the molecular level.
  • To provide a molecular motion picture of RNA helix opening.

Main Methods:

  • Atomistic pulling simulations were used to enforce the base opening process.
  • A novel reweighting scheme was developed to reconstruct free-energy profiles along reaction coordinates like solvation.
  • The approach was systematically applied to different base-pair combinations.

Main Results:

  • A detailed molecular motion picture of RNA helix opening was generated.
  • The free-energy profiles for base pair opening were reconstructed.
  • The results were validated against extensive experimental observations.
  • A link between RNA dynamics and enzyme-dependent unwinding mechanisms was established.

Conclusions:

  • The intrinsic dynamics of RNA duplexes have been elucidated.
  • These dynamics can rationalize the directionality observed in RNA-processing molecular machineries.
  • The study provides a molecular basis for understanding RNA conformational changes.