Related Experiment Video
Updated: May 22, 2026

07:27
Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
Published on: April 30, 2010
Pathways of mammalian replication fork restart
Eva Petermann1, Thomas Helleday
1University of Birmingham, UK. e.petermann@bham.ac.uk
Nature Reviews. Molecular Cell Biology
|September 16, 2010
Summary
Mammalian cells possess distinct pathways for restarting stalled DNA replication forks. These pathways involve accessory proteins and mechanisms like homologous recombination, highlighting complex DNA repair processes.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- DNA replication is crucial for cell division and genome stability.
- Replication forks can stall due to various stress factors, requiring restart mechanisms.
- Understanding replication restart is key to comprehending DNA repair and disease.
Purpose of the Study:
- To elucidate the mechanisms of mammalian replication fork restart.
- To identify proteins involved in restarting stalled replication forks.
- To explore different models of replication fork restart.
Main Methods:
- Single-molecule analyses of DNA replication.
- Investigating the role of non-core replication machinery proteins.
- Analyzing pathways involving DNA helicases, nucleases, and homologous recombination.
Main Results:
- Single-molecule studies reveal advanced insights into mammalian replication restart.
- Proteins outside the core replication machinery facilitate efficient restart of stalled forks.
- Evidence supports the existence of bona fide replication fork restart pathways in mammalian cells.
Conclusions:
- Mammalian cells have specialized pathways for replication restart.
- These pathways involve accessory proteins and diverse molecular players.
- Models of restart incorporate DNA helicases, nucleases, homologous recombination, and double-strand break formation.
More Related Videos
Related Concept Videos
Replication in Eukaryotes
Overview
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...
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
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...
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.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
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...

