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Related Concept Videos

Restarting Stalled Replication Forks02:37

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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 DNA Replication Fork01:02

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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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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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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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H2BK120ub and its reader RNF169 sequentially regulate replication fork remodeling and stability.

Filip D Duzanic1, Vaishnavi Mohana-Natarajan1,2, Samuele Fisicaro1

  • 1University of Zurich, Institute of Molecular Cancer Research, 8057, Zurich, Switzerland.

The EMBO Journal
|October 28, 2025
PubMed
Summary
This summary is machine-generated.

Histone H2B ubiquitination (H2BK120ub) is crucial for DNA replication fork dynamics in human cells. The RNF20-H2BK120ub-RNF169 pathway regulates fork stability and protects DNA during replication stress.

Keywords:
DNA Replication Stress ResponseFork Plasticity and RestartHistone H2B UbiquitinationRNF169RNF20/RNF40

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Histone ubiquitination, specifically H2BK120ub, is vital for DNA processes like transcription and repair.
  • Its role in human DNA replication remains largely uncharacterized.
  • This study investigates the function of H2BK120ub in replication fork dynamics.

Purpose of the Study:

  • To elucidate the role of H2BK120ub in human DNA replication fork dynamics.
  • To identify the key proteins involved in regulating H2BK120ub at replication forks.
  • To understand how this modification impacts the response to replication stress.

Main Methods:

  • Immunofluorescence to detect H2BK120ub at replication forks.
  • Analysis of replication fork progression and stability in cells with altered RNF20 or RNF169 expression.
  • Investigating the dependence on ATR and RAD51 for H2BK120ub accumulation.
  • Assessing the impact on BRCA2-deficient cells.

Main Results:

  • H2BK120ub is present at replication forks and increases under replication stress, dependent on ATR and RAD51.
  • Loss of RNF20 leads to unrestrained fork progression by RECQ1 and impaired fork reversal, which stabilizes forks in BRCA2-deficient cells.
  • RNF169 acts as a reader of H2BK120ub at stalled forks, preventing excessive nucleolytic degradation of nascent DNA.

Conclusions:

  • RNF20, H2BK120ub, and RNF169 are critical regulators of the replication stress response in human cells.
  • This pathway controls replication fork plasticity and stability.
  • The findings reveal a novel mechanism for maintaining genome integrity during replication stress.