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Related Concept Videos

The DNA Replication Fork01:02

The DNA Replication Fork

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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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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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DNA Helicases00:55

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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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Homologous Recombination02:31

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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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Updated: Dec 11, 2025

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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The RECQL helicase prevents replication fork collapse during replication stress.

Bente Benedict1, Marit Ae van Bueren1, Frank Pa van Gemert1

  • 1Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Life Science Alliance
|August 22, 2020
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Summary

Replication stress in cancer cells relies on RECQL helicase to protect DNA. Loss of RECQL leads to DNA breaks, highlighting its potential as a cancer therapy target.

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Area of Science:

  • Molecular biology
  • Cancer research
  • Genetics

Background:

  • Most tumors lose the G1/S phase checkpoint, becoming insensitive to antigrowth signals.
  • Loss of G1/S control disrupts DNA replication, causing slow fork progression and stalling.
  • Cancer cells may depend on pathways that mitigate replication stress consequences.

Purpose of the Study:

  • Identify vulnerabilities in cells experiencing replication stress.
  • Investigate the role of RECQL helicase in DNA replication under stress.

Main Methods:

  • Conducted an shRNA-based genetic screen to identify essential genes under replication stress.
  • Assessed the impact of RECQL knockdown on DNA double-strand break (DSB) formation in cancer cells.

Main Results:

  • The RECQL helicase was found to be essential under replication stress conditions.
  • RECQL protects stalled replication forks from MRE11-dependent double-strand break (DSB) formation.
  • RECQL knockdown increased DNA DSBs in various cancer cell types.

Conclusions:

  • RECQL is critical for maintaining DNA synthesis during replication stress.
  • RECQL's role in protecting against DNA damage makes it a potential therapeutic target for cancer.