Related Experiment Video
Updated: Sep 12, 2025
07:37
Author Spotlight: Unraveling the Dynamics of Eukaryotic DNA Replication Through Single-Molecule Visualization
Published on: September 27, 2024
1.7K
The Ski2 helicase ASCC3 unwinds DNA upon fork stalling to control replication stress responses
Shixin Cui1, Nicole L Batenburg1, Yan Coulombe2
1Department of Biology, McMaster University, Hamilton, Ontario, Canada L8S 4K1.
Biorxiv : the Preprint Server for Biology
|August 8, 2025
Summary
Activating Signal Co-integrator 1 complex subunit 3 (ASCC3) promotes genomic stability by unwinding DNA at stalled replication forks. ASCC3 prevents DNA breaks and mis-segregation during replication stress.
Area of Science:
- Molecular Biology
- Genomics
- DNA Replication
Background:
- Activating Signal Co-integrator 1 complex subunit 3 (ASCC3) is a helicase implicated in DNA repair and ribosome quality control.
- ASCC3's role in replication stress response and its association with stalled forks are not well understood.
Purpose of the Study:
- To elucidate the function of ASCC3 in response to replication stress.
- To investigate the mechanisms by which ASCC3 maintains genomic stability.
Main Methods:
- Investigated ASCC3 recruitment to stalled replication forks via its interaction with ASCC2.
- Analyzed ASCC3's DNA unwinding activity and its role in fork reversal.
- Examined ASCC3's interaction with RPA and its effect on ATR activation.
- Assessed ASCC3's impact on RAD51-mediated recombination and chromosome stability.
Main Results:
- ASCC3 is recruited to stalled forks by ASCC2, dependent on PCNA ubiquitylation.
- ASCC3 unwinds DNA, promoting fork reversal and stimulating RPA accumulation for ATR activation.
- ASCC3 antagonizes RAD51-mediated recombination, preventing DNA breaks and mis-segregation.
Conclusions:
- ASCC3 plays a critical, previously uncharacterized role in multiple replication stress responses.
- ASCC3 is essential for maintaining genomic stability by managing DNA unwinding, fork reversal, and suppressing recombination.
Related Concept Videos
02:37Restarting Stalled Replication Forks
5.9K
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,...
5.9K
01:02The DNA Replication Fork
36.8K
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...
36.8K
02:37DNA Damage can Stall the Cell Cycle
9.3K
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...
9.3K
00:55DNA Helicases
22.2K
DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
22.2K
02:02DNA Topoisomerases
32.1K
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
32.1K
02:38S-Cdk Initiates DNA Replication
4.8K
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...
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.8K