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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, a...

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, a...

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 forks, one in...

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 forks, one in...

Homologous Recombination

Homologous Recombination

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...

DNA Damage can Stall the Cell Cycle

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

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Related Experiment Video

Updated: May 11, 2026

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

Rescuing stalled or damaged replication forks.

Joseph T P Yeeles¹, Jérôme Poli, Kenneth J Marians

¹Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Cold Spring Harbor Perspectives in Biology

|May 3, 2013

Summary

This summary is machine-generated.

Prokaryotes and eukaryotes use similar DNA replication fork restart mechanisms, like repriming and fork regression, to maintain genome stability. Eukaryotic restart involves chromatin and regulatory pathways, differing from prokaryotes.

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Last Updated: May 11, 2026

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

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Published on: April 29, 2010

Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay

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Area of Science:

Molecular Biology
Genetics
Cell Biology

Background:

DNA replication is essential for cell division and genome integrity.
Stalled or collapsed replication forks pose a significant threat to genomic stability.
Prokaryotic and eukaryotic cells possess intricate mechanisms to resolve replication stress.

Purpose of the Study:

To elucidate the conserved and distinct mechanisms of replication fork restart in prokaryotes and eukaryotes.
To highlight the roles of repriming and fork regression in fork recovery.
To compare the regulatory pathways governing fork restart across different life domains.

Main Methods:

Comparative genomics analysis to identify conserved and divergent factors.
Biochemical assays to study the function of key proteins in fork restart.
Cellular imaging techniques to visualize fork dynamics and restart intermediates.

Main Results:

Repriming on the leading strand and fork regression are critical for stalled fork recovery in both bacteria and eukaryotes.
Despite functional similarities, the specific protein factors involved in these processes show limited conservation.
Eukaryotic fork restart operates within the context of chromatin and is subject to complex regulatory networks.

Conclusions:

DNA replication fork restart mechanisms are ancient and fundamentally conserved across prokaryotes and eukaryotes.
Understanding these pathways is crucial for comprehending genome stability maintenance.
Differences in chromatin and regulatory control highlight unique adaptations in eukaryotic fork restart.