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Related Concept Videos

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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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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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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DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
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Replication in Eukaryotes01:29

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In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
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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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Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
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Helicases in R-loop Formation and Resolution.

Shizhuo Yang1, Lacey Winstone1, Sohaumn Mondal1

  • 1Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

The Journal of Biological Chemistry
|October 1, 2023
PubMed
Summary

Helicases play dual roles in R-loop metabolism, promoting their formation and resolution. Understanding these enzymes is crucial for targeting R-loop associated diseases and challenges in drug discovery.

Keywords:
CRISPRR-loopR-loop formationR-loop resolutionRNA-DNA hybridcancerdiseasehelicase

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • R-loop structures, composed of RNA-DNA hybrids and single-stranded DNA, are increasingly recognized due to CRISPR technology.
  • These structures are involved in critical cellular processes like transcription, DNA repair, and telomere maintenance.

Purpose of the Study:

  • To review the current understanding of helicases' roles in R-loop metabolism.
  • To highlight the challenges in developing drugs that target R-loop helicases.

Main Methods:

  • Literature review of studies on helicase function in R-loop dynamics.
  • Analysis of helicase activities including unwinding and strand-annealing.
  • Identification of specific helicases involved in R-loop formation and resolution.

Main Results:

  • Helicases can both promote R-loop formation via strand-annealing and resolve them through unwinding activity.
  • Numerous helicases (e.g., SETX, AQR, WRN, BLM, RTEL1, PIF1, FANCM, ATRX, CasDinG, DEAD/H-box proteins) resolve R-loops.
  • Other helicases (e.g., Cas3, UPF1) stimulate R-loop formation, while some (e.g., DDX1, DDX17, DHX9) participate in both processes.

Conclusions:

  • Helicases are key regulators of R-loop metabolism, exhibiting context-dependent roles in their biogenesis and resolution.
  • Targeting R-loop helicases presents therapeutic opportunities but also significant drug discovery challenges.