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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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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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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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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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Related Experiment Video

Updated: Jul 25, 2025

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
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Nuclear myosin VI maintains replication fork stability.

Jie Shi1, Kristine Hauschulte1, Ivan Mikicic1

  • 1Institute of Molecular Biology gGmbH (IMB), Ackermannweg 4, D - 55128, Mainz, Germany.

Nature Communications
|June 24, 2023
PubMed
Summary
This summary is machine-generated.

Myosin VI stabilizes stalled DNA replication forks in the nucleus, cooperating with WRNIP1 to prevent degradation. This nuclear role is crucial during replication stress, independent of cytoplasmic myosin VI.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The actin cytoskeleton is vital for cellular structure and dynamics.
  • The presence and role of filamentous actin within the cell nucleus remain debated.
  • Understanding nuclear actin functions is key to cellular plasticity.

Purpose of the Study:

  • To investigate the role of the actin-based motor myosin VI in the nucleus.
  • To determine myosin VI's function during DNA replication stress.
  • To clarify the contribution of nuclear versus cytoplasmic myosin VI pools.

Main Methods:

  • Utilized functionalized affinity probes to manipulate nuclear myosin VI levels.
  • Investigated the interaction of myosin VI with stalled replication forks.
  • Assessed the protective role of myosin VI against nucleolytic degradation.

Main Results:

  • Myosin VI directly associates with stalled or reversed DNA replication forks.
  • Myosin VI cooperates with Werner helicase interacting protein 1 (WRNIP1).
  • This complex protects replication intermediates from DNA2-mediated degradation.
  • Evidence supports a direct nuclear function of myosin VI during replication stress.

Conclusions:

  • Myosin VI plays a critical role in stabilizing stalled replication forks within the nucleus.
  • Nuclear myosin VI, not the cytoplasmic pool, is essential for the replication stress response.
  • The findings resolve controversies regarding nuclear actin motor functions.