Related Experiment Video
Updated: Jun 27, 2026
10:59
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Mechanisms of dealing with DNA damage-induced replication problems
Magda Budzowska1, Roland Kanaar
1Department of Cell Biology & Genetics, Cancer Genomics Center, Rotterdam, The Netherlands.
Cell Biochemistry and Biophysics
|November 27, 2008
Summary
Cells must accurately duplicate DNA each S phase. DNA lesions stall replication forks, requiring checkpoint signaling and specialized pathways like homologous recombination and translesion synthesis for restart and cell survival.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Cellular DNA replication is crucial for inheritance, demanding high precision.
- DNA lesions pose a significant threat to replication accuracy and efficiency.
- Replicative DNA polymerases halt at DNA lesions, potentially leading to replication fork stalling.
Purpose of the Study:
- To review the cellular response to replication perturbation caused by DNA lesions.
- To explain the roles of checkpoint signaling and replication restart pathways in maintaining genome stability.
Main Methods:
- Review of existing literature on DNA replication, DNA repair, and cell cycle control.
- Analysis of the mechanisms involved in checkpoint activation and replication restart pathways.
Main Results:
- Checkpoint signaling delays cell cycle progression, providing time for DNA damage repair.
- Replication restart is facilitated by two main pathways: homologous recombination (error-free) and translesion synthesis (error-prone).
Conclusions:
- A coordinated cellular response involving checkpoint activation and replication restart pathways is essential for cell survival and fitness when replication forks are stalled.
- These pathways ensure accurate genome duplication despite the presence of DNA damage.
Related Concept Videos
01:02The 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...
01:02The 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...
02:37Restarting 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...
02:37Restarting 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...
02:36DNA 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...
02:36DNA 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...