Related Experiment Video
Updated: May 14, 2026
07:11
Laser Micro-Irradiation to Study DNA Recruitment During S Phase
Published on: April 16, 2021
SMC1-mediated intra-S-phase arrest facilitates bocavirus DNA replication
Yong Luo1, Xuefeng Deng, Fang Cheng
1Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Journal of Virology
|February 1, 2013
Summary
Minute virus of canines (MVC) replication requires host DNA damage response (DDR). MVC infection triggers an intra-S-phase arrest, regulated by ATM-SMC1 signaling, essential for viral DNA replication.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- Minute virus of canines (MVC), a Bocavirus, requires host DNA damage response (DDR) for DNA replication.
- The precise mechanism linking DDR to MVC replication remains unclear.
Purpose of the Study:
- To elucidate the mechanism by which DDR facilitates MVC DNA replication.
- To identify key host factors involved in DDR-induced viral replication.
Main Methods:
- Investigated MVC infection in host cells.
- Analyzed cell cycle progression, focusing on intra-S-phase arrest.
- Utilized gene knockdown and dominant-negative mutants for ATM (ataxia telangiectasia-mutated kinase) and SMC1 (structural maintenance of chromosomes 1).
- Examined the role of the Mre11-Rad50-Nbs1 (MRN) complex.
Main Results:
- MVC infection induces an intra-S-phase arrest, slowing host DNA replication and recruiting replication factors for viral use.
- This arrest is mediated by ATM signaling in a p53-independent manner.
- SMC1 is identified as a crucial regulator; its inhibition blocks both the arrest and viral replication.
- The intra-S-phase arrest is triggered by replicating viral genomes interacting with the MRN complex, not by damaged DNA or viral proteins.
Conclusions:
- A feedback loop between MVC replication and intra-S-phase arrest, orchestrated by ATM-SMC1 signaling, is critical for viral DNA replication.
- This study reveals a novel mechanism of DNA virus-host interaction where DDR signaling is co-opted for viral replication.
Related Concept Videos
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
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...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.