Related Experiment Video
Updated: Oct 17, 2025
07:55
Visualization of DNA Repair Proteins Interaction by Immunofluorescence
Published on: June 26, 2020
10.5K
The Safe Path at the Fork: Ensuring Replication-Associated DNA Double-Strand Breaks are Repaired by Homologous
Jac A Nickoloff1, Neelam Sharma1, Lynn Taylor1
1Department of Environmental and Radiological Health Sciences, Colorado State University, Ft. Collins, CO, United States.
Frontiers in Genetics
|October 14, 2021
Summary
Cells face replication stress, challenging DNA replication. This review highlights how DNA repair mechanisms, particularly homologous recombination, promote genome stability by managing stressed replication forks and preventing cancer.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Accurate DNA replication and segregation are crucial for maintaining genome stability and preventing cancer.
- Replication forks can stall due to DNA lesions, difficult sequences, or chemical inhibitors, leading to replication stress.
- Cells activate DNA damage response pathways to cope with replication stress, influencing cell cycle progression, repair, and survival.
Purpose of the Study:
- To review mechanisms that maintain genome stability under replication stress.
- To highlight the role of DNA resection and homologous recombination in restarting stalled replication forks.
- To discuss how these processes prevent genome rearrangements and cancer development.
Main Methods:
- Literature review of molecular and cellular mechanisms.
- Analysis of DNA damage response pathways.
- Focus on replication fork dynamics and repair processes.
Main Results:
- Replication stress challenges fork progression, leading to fork collapse or reversal.
- Stressed forks can be rescued by various mechanisms including fork reversal, generating single-ended double-strand breaks (seDSBs).
- Homologous recombination (HR) is critical for restarting collapsed forks via DNA resection, preventing detrimental non-homologous end-joining (NHEJ).
Conclusions:
- Promoting DNA resection of seDSBs is vital for accurate fork restart by HR.
- Effective management of replication stress by HR maintains genome stability and suppresses tumorigenesis.
- Understanding these pathways offers insights into cancer prevention and therapy.
Related Concept Videos
02:31Homologous Recombination
55.6K
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...
55.6K
02:04Fixing Double-strand Breaks
13.2K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
13.2K
02:25Overview of DNA Repair
32.2K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
32.2K
01:36Mismatch Repair
41.0K
Overview
41.0K
02:10Translesion DNA Polymerases
10.3K
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.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
10.3K
02:37Restarting Stalled Replication Forks
6.0K
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,...
6.0K