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Restarting Stalled Replication Forks

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,...

The DNA Replication Fork

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...

Replication in Prokaryotes

Replication in Prokaryotes

DNA replication has three main steps: initiation, elongation, and termination. Replication in prokaryotes begins when initiator proteins bind to the single origin of replication (ori) on the cell's circular chromosome. Replication then proceeds around the entire circle of the chromosome in each direction from the two replication forks, resulting in two DNA molecules.
Many Proteins Work Together to Replicate the Chromosome
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Replication in Eukaryotes

Replication in Eukaryotes

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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The Replisome

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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.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...

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Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
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Related Experiment Video

Updated: Jul 9, 2025

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

Published on: April 29, 2010

Processing of stalled replication forks in Bacillus subtilis.

Begoña Carrasco¹, Rubén Torres¹, María Moreno-Del Álamo¹

¹Department of Microbial Biotechnology, Centro Nacional de Biotecnología, CNB-CSIC, 3 Darwin Str, 28049 Madrid, Spain.

FEMS Microbiology Reviews

|December 5, 2023

Summary

Bacillus subtilis uses various proteins to overcome replication stress and maintain genomic stability. These proteins help restart DNA synthesis after replication fork arrest, preventing genomic instability.

Keywords:

DNA damage tolerance RNA polymerase hub RecA hub SsbA hub fork reversal replisome disassembly template switching

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Last Updated: Jul 9, 2025

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

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Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion

Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion

Published on: September 13, 2024

Area of Science:

Molecular Biology
Genomics
Microbiology

Background:

Accurate DNA replication and transcription are vital for genomic stability.
Cells possess mechanisms to manage impaired replication fork progression.
Bacillus subtilis is a model organism for studying replication stress response.

Conclusions:

A complex network of proteins in Bacillus subtilis facilitates the restart of DNA replication following stress.
These pathways are critical for maintaining genomic integrity in the face of replication impediments.
Understanding these mechanisms provides insights into fundamental cellular processes for genome preservation.